☆ 4.5 Article

The pyruvate dehydrogenase complex: Life's essential, vulnerable and druggable energy homeostat

MITOCHONDRION (2023)

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A preoptic neuronal population controls fever and appetite during sickness

Jessica A. Osterhout et al.

Summary: This study identifies a previously uncharacterized population of neurons in the brain that are activated after infection, playing a crucial role in generating fever response and other sickness symptoms. By examining gene expression and electrophysiological measurements, the researchers uncover a mechanism where these neurons are influenced by immune signals released by non-neuronal cells during infection and are functionally connected to brain areas controlling body temperature and appetite.

NATURE (2022)

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Article Neurosciences

Metabolic lactate production coordinates vasculature development and progenitor behavior in the developing mouse neocortex

Xiaoxiang Dong et al.

Summary: The study shows that proliferative neural progenitors in the developing neocortex preferentially undergo anaerobic glycolysis, producing a high level of lactate that coordinately regulates vascular outgrowth and progenitor behavior. The findings reveal the metabolic regulation of neural progenitor behavior and vessel growth in neocortical development.

NATURE NEUROSCIENCE (2022)

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Article Multidisciplinary Sciences

Noncanonical PDK4 action alters mitochondrial dynamics to affect the cellular respiratory status

Themis Thoudam et al.

Summary: The study reveals that PDK4 plays a crucial role in promoting rapid mitochondrial fragmentation in response to ETC toxins, and overexpression of PDK4 can induce mitochondrial fission even in the absence of mitochondrial stress. The investigation also identifies SEPT2 as a key effector molecule for PDK4 to regulate mitochondrial fission through DRP1 at the interface of cellular bioenergetics and mitochondrial dynamics.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Multidisciplinary Sciences

Interleukin-17 governs hypoxic adaptation of injured epithelium

Piotr Konieczny et al.

Summary: Mammalian cells activate HIFs to survive in low-oxygen environments, but injury-induced hypoxia is unable to activate HIF1 alpha. However, IL-17A derived from ROR gamma t(+) gamma delta T cells can activate HIF1 alpha. The IL-17A-HIF1 alpha axis promotes glycolysis for wound healing in epithelial cells, and loss of IL-17RC, HIF1 alpha, or blockade of glycolysis disrupts the repair process. These findings highlight the interconnectedness of inflammation, metabolism, and migration programs, as well as the role of immune cell-derived inputs in cellular adaptation to hypoxic stress during repair.

SCIENCE (2022)

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Article Medicine, Research & Experimental

Dichloroacetate improves systemic energy balance and feeding behavior during sepsis

Tae Seok Oh et al.

Summary: This study reveals the relationship between sepsis and systemic metabolic abnormalities, as well as the interaction between liver and systemic metabolic reprogramming. It was found that sepsis leads to an increase in circulating free fatty acids and acylcarnitines, but a decrease in levels of amino acids and carbohydrates, resulting in a drastic shift in systemic fuel preference. Furthermore, glycine deficiency was identified as a common abnormality in the plasma and liver during sepsis, and the septic liver may contribute to systemic glycine deficiency by downregulating genes involved in glycine synthesis. Moreover, the study found that the intraperitoneal injection of the PDK inhibitor dichloroacetate reversed various metabolic abnormalities induced by sepsis, partly through the restoration of hepatic fuel metabolism.

JCI INSIGHT (2022)

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Review Chemistry, Medicinal

Cytotoxic derivatives of dichloroacetic acid and some metal complexes

Mohammad Hossain et al.

Summary: This study provides an overview of several studies on dichloroacetic acid (DCA) and its derivatives. While DCA itself has low cytotoxicity, modifications have been made to produce potent cytotoxins. Hybrid molecules created by combining DCA with other bioactive molecules that have different modes of action show promise as potential anticancer agents. The review also emphasizes the importance of formulating the described bioactive compounds.

ARCHIV DER PHARMAZIE (2022)

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Article Multidisciplinary Sciences

Oncometabolite D-2HG alters T cell metabolism to impair CD8(+) T cell function

Giulia Notarangelo et al.

Summary: Gain-of-function mutations in IDH result in the production of oncometabolite D-2HG, which promotes tumorigenesis by affecting the metabolism and antitumor functions of CD8(+) T cells.

SCIENCE (2022)

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Review Endocrinology & Metabolism

Understanding lactate sensing and signalling

Michelangelo Certo et al.

Summary: Metabolites generated from cellular and tissue metabolism, such as lactate, have been found to have signaling functions and play important roles in various physiological and pathological processes.

TRENDS IN ENDOCRINOLOGY AND METABOLISM (2022)

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Article Multidisciplinary Sciences

Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2

Tianshi Feng et al.

Summary: Adipocyte tissue macrophages (ATM) are recruited and activated in obesity. Adipocytes release lactate as a signal of inflammation, which can enhance obesity-associated inflammation through direct binding with PHD2. This study reveals the critical role of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose tissue and identifies PHD2 as a direct sensor of lactate, linking chronic inflammation and energy metabolism.

NATURE COMMUNICATIONS (2022)

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Article Geriatrics & Gerontology

Pyruvate dehydrogenase kinase 4 promotes ubiquitin-proteasome system-dependent muscle atrophy

Ibotombi Singh Sinam et al.

Summary: This study reveals that PDK4 mediates dexamethasone-induced muscle atrophy by phosphorylating and degrading myogenin. The findings suggest that PDK4 may be a potential therapeutic target for muscle wasting.

JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE (2022)

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Article Cardiac & Cardiovascular Systems

Detection of increased pyruvate dehydrogenase flux in the human heart during adenosine stress test using hyperpolarized [1-13C]pyruvate cardiovascular magnetic resonance imaging

Steen Hylgaard Joergensen et al.

Summary: This study combines adenosine stress testing with HP [1-C-13]pyruvate CMR to detect cardiac metabolism in healthy individuals. The results demonstrate an increase in myocardial perfusion and metabolism during stress.

JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE (2022)

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Article Endocrinology & Metabolism

PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing

Egle Danileviciute et al.

Summary: In this study, the researchers found that the protein DJ-1 plays a crucial role in regulating PDH activity in T-reg cells, especially in aged mice. This discovery provides new insights into the regulation of the PDH complex and suggests the DJ-1-PDHB axis as a potential target for maintaining or re-establishing T-reg homeostasis.

NATURE METABOLISM (2022)

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Review Physiology

Mitochondria as mediators of systemic inflammation and organ cross talk in acute kidney injury

Mark Hepokoski et al.

Summary: Acute kidney injury (AKI) is an inflammatory disease that can cause remote organ failures. Mitochondrial injury in AKI leads to the release of damage-associated molecular patterns, which activate systemic inflammation. Current evidence suggests that modulating extracellular mitochondrial damage-associated molecular patterns may have the potential to improve remote organ failures caused by AKI.

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY (2022)

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Article Endocrinology & Metabolism

MAPK signalling-induced phosphorylation and subcellular translocation of PDHE1 alpha promotes tumour immune evasion

Yajuan Zhang et al.

Summary: This study reveals a mechanism through which phosphorylation-dependent subcellular translocation of PDHE1 alpha promotes tumor immune evasion.

NATURE METABOLISM (2022)

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Article Gastroenterology & Hepatology

PPARγ Coactivator-1α Suppresses Metastasis of Hepatocellular Carcinoma by Inhibiting Warburg Effect by PPARγ-Dependent WNT/β-Catenin/Pyruvate Dehydrogenase Kinase Isozyme 1 Axis

Qiaozhu Zuo et al.

Summary: The study revealed that PGC1 alpha is down-regulated in HCC, and its low expression is associated with poor prognosis, vascular invasion, and larger tumor size. PGC1 alpha inhibits HCC metastasis by regulating the WNT/beta-catenin/PDK1 axis.

HEPATOLOGY (2021)

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Article Endocrinology & Metabolism

Neuroprotective role of lactate in rat neonatal hypoxia-ischemia

Helene Roumes et al.

Summary: Lactate has shown neuroprotective effects in a neonatal hypoxia-ischemia model, reducing brain lesion volume rapidly and efficiently. Lactate metabolism plays a key role in this protection, and lactate administration holds promise as an effective therapy for neonatal HI insult.

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM (2021)

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Article Biochemistry & Molecular Biology

Lung Myofibroblasts Promote Macrophage Profibrotic Activity through Lactate-induced Histone Lactylation

Huachun Cui et al.

Summary: This study demonstrates that in lung fibrosis, myofibroblasts enhance glycolysis to produce lactate, which regulates the pathogenic phenotype of alveolar macrophages. Lactate induces profibrotic gene expression in macrophages, promoting the fibrotic process.

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY (2021)

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Review Endocrinology & Metabolism

Loss of metabolic flexibility as a result of overexpression of pyruvate dehydrogenase kinases in muscle, liver and the immune system: Therapeutic targets in metabolic diseases

Jae-Han Jeon et al.

Summary: Good health relies on maintaining metabolic flexibility, which is influenced by the regulation of a large number of enzymes, particularly the pyruvate dehydrogenase complex (PDC) in carbohydrate metabolism. The flexibility in PDC regulation depends on the balance between pyruvate dehydrogenase kinases (PDKs) and pyruvate dehydrogenase phosphatases. Overexpression of PDK4 leading to PDC inactivation contributes to hyperglycemia and serious health issues like diabetes. Other diseases such as cancers, non-alcoholic fatty liver disease, and sepsis also show loss of regulatory flexibility in PDC.

JOURNAL OF DIABETES INVESTIGATION (2021)

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Review Genetics & Heredity

Extreme heterogeneity of human mitochondrial DNA from organelles to populations

James B. Stewart et al.

Summary: Deep resequencing has revealed extreme genetic variation in mitochondrial genomes at multiple levels, shedding light on the origins of human mitochondrial DNA mutations and their impact on rare and common human diseases, including cancer.

NATURE REVIEWS GENETICS (2021)

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Article Cell Biology

Yin Yang 1-induced LINC00667 up-regulates pyruvate dehydrogenase kinase 1 to promote proliferation, migration and invasion of cholangiocarcinoma cells by sponging miR-200c-3p

Jinglin Li et al.

Summary: The study showed that LINC00667 is highly expressed in cholangiocarcinoma (CCA) and promotes CCA development by regulating the YY1/LINC00667/miR-200c-3p/PDK1 axis. Suppression of LINC00667 inhibits proliferation, migration, and invasion of CCA cells, suggesting a novel therapeutic strategy for CCA treatment.

HUMAN CELL (2021)

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Article Biochemistry & Molecular Biology

The key role of Warburg effect in SARS-CoV-2 replication and associated inflammatory response

Philippe Icard et al.

Summary: The current mortality due to Covid-19 pandemic highlights the lack of effective treatment, with research suggesting that the replication of SARS-CoV-2 may rely on altered glucose metabolism similar to the Warburg effect in cancer. Inhibiting two key signaling pathways that sustain aerobic glycolysis could potentially inhibit virus replication. Understanding the role of the Warburg effect in Covid-19 could be crucial in developing strategies to reduce infectivity and immune response.

BIOCHIMIE (2021)

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Article Oncology

PDK4 promotes tumorigenesis and cisplatin resistance in lung adenocarcinoma via transcriptional regulation of EPAS1

Shuo Yu et al.

Summary: This study identified PDK4 as a key upregulated kinase in cisplatin-resistant lung adenocarcinoma cells, where its overexpression was directly linked to chemoresistance and enhanced tumor cell growth through the regulation of EPAS1 expression. High expression of PDK4 was also correlated with poor prognosis in patients with lung adenocarcinoma.

CANCER CHEMOTHERAPY AND PHARMACOLOGY (2021)

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Article Cell Biology

The Source of Glycolytic Intermediates in Mammalian Tissues

Tara TeSlaa et al.

Summary: Glycolysis is central to organismal metabolism, with circulating glucose and intracellular glycogen being the main sources of glycolytic intermediates. Gluconeogenesis also contributes to glycolysis to a lesser extent. Different tissues show variations in utilizing circulating glucose for glycolysis, with most tissues relying on glycogen breakdown for glycolytic intermediates. Overall, the body slowly breaks down internal glycogen stores while select tissues rapidly catabolize circulating glucose for oxidation.

CELL METABOLISM (2021)

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Article Cell Biology

The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure

Ahmad A. Cluntun et al.

Summary: The metabolic rewiring of cardiomyocytes, including decreased mitochondrial pyruvate oxidation and increased lactate export, is a key feature of heart failure. The mitochondrial pyruvate carrier (MPC) and the cellular lactate exporter monocarboxylate transporter 4 (MCT4) play pivotal roles in this metabolic axis. Alteration of the pyruvate-lactate axis is a fundamental and early feature of cardiac hypertrophy and failure.

CELL METABOLISM (2021)

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Article Endocrinology & Metabolism

3-Hydroxybutyrate administration elevates plasma parathyroid hormone in a pilot human randomized, controlled, cross over trial

Mads Svart et al.

Summary: This study examined the impact of exogenous 3OHB administration on bone metabolism, specifically on PTH, calcium/phosphate homeostasis, and bone turnover markers. It was found that 3OHB infusion led to an increase in PTH concentration, a decrease in phosphate levels, and an increase in markers of bone resorption. These findings suggest a potential negative effect of 3OHB on bone health, which warrants further investigation in future studies.

BONE (2021)

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Article Neurosciences

Satellite glia as a critical component of diabetic neuropathy: Role of lipocalin-2 and pyruvate dehydrogenase kinase-2 axis in the dorsal root ganglion

Anup Bhusal et al.

Summary: Research shows that diabetes upregulates lipocalin-2 (LCN2) in satellite glial cells (SGCs) within the dorsal root ganglia, leading to increased expression of pyruvate dehydrogenase kinase-2 (PDK2) and production of lactic acid, playing a crucial role in the pathogenesis of diabetic peripheral neuropathy (DPN).

GLIA (2021)

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Article Endocrinology & Metabolism

PDK2 Deficiency Prevents Ovariectomy-Induced Bone Loss in Mice by Regulating the RANKL-NFATc1 Pathway During Osteoclastogenesis

Ji-Min Lee et al.

Summary: In this study, inhibition of PDK2 was found to prevent osteoporosis in estrogen-deficient mice by reducing aberrant osteoclast activation. These findings suggest that PDK2 inhibitors might be repurposed for the therapy of estrogen deficiency-induced osteoporosis.

JOURNAL OF BONE AND MINERAL RESEARCH (2021)

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Article Biochemistry & Molecular Biology

Increased demand for NAD+ relative to ATP drives aerobic glycolysis

Alba Luengo et al.

Summary: Increasing the activity of the pyruvate dehydrogenase complex impairs cell proliferation by reducing the NAD(+)/NADH ratio, which is caused by increased mitochondrial membrane potential. When demand for NAD(+) exceeds the demand for ATP in cells, aerobic glycolysis is promoted despite available oxygen.

MOLECULAR CELL (2021)

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Article Multidisciplinary Sciences

Restoring metabolism of myeloid cells reverses cognitive decline in ageing

Paras S. Minhas et al.

Summary: Ageing is characterized by chronic pro-inflammatory responses that affect various aspects of health, including the brain. The study shows that in ageing mice, myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E-2 (PGE(2)), leading to maladaptive pro-inflammatory responses. By inhibiting myeloid EP2 signalling, it is possible to reverse cognitive ageing and restore youthful immune functions.

NATURE (2021)

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Review Cell Biology

NAD+ metabolism and its roles in cellular processes during ageing

Anthony J. Covarrubias et al.

Summary: NAD(+) is a crucial coenzyme in redox reactions and plays a pivotal role in energy metabolism. Its levels decline with age, and raising NAD(+) levels is being explored as a potential strategy to extend human lifespan and healthspan. NAD(+) influences key cellular processes and functions, including metabolic pathways, DNA repair, and cellular senescence, with implications for healthy aging and age-related diseases.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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Article Biophysics

Hyperpolarized magnetic resonance shows that the anti-ischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved post-ischemic function in the diabetic heart

Dragana Savic et al.

Summary: The study investigated the effects of meldonium on cardiac metabolism in diabetic rats, revealing an increase in pyruvate dehydrogenase flux and improvement in cardiac recovery after ischemia.

NMR IN BIOMEDICINE (2021)

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Article Oncology

Phosphorylated form of pyruvate dehydrogenase α1 mediates tumor necrosis factor α-induced glioma cell migration

Zijun Yang et al.

Summary: The study demonstrated that p-PDHA1 levels increased with the grade of glioma, and mediated TNF-alpha induced cell migration in glioma cells. These results suggest that p-PDHA1 plays a crucial role in glioma cell migration and development.

ONCOLOGY LETTERS (2021)

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Article Multidisciplinary Sciences

Emr1 regulates the number of foci of the endoplasmic reticulum-mitochondria encounter structure complex

Faiz Rasul et al.

Summary: This study reveals the crucial role of the previously uncharacterized mitochondrial membrane protein Emr1 in regulating the number of ERMES foci, with its absence significantly decreasing the foci number, affecting mitochondrial morphology and segregation. Emr1 interacts with the ERMES core component Mdm12 and is essential for ERMES functions, shedding light on the dynamic regulation of endoplasmic reticulum-mitochondria communication.

NATURE COMMUNICATIONS (2021)

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Article Endocrinology & Metabolism

Kruppel-like factor 15 regulates fuel switching between glucose and fatty acids in brown adipocytes

Yuko Nabatame et al.

Summary: The study highlights the importance of KLF15 in regulating fuel switching between glucose and fatty acids in brown adipose tissue. This is achieved through its impact on fatty acid and glucose oxidation, as well as pyruvate dehydrogenase complex activity in BAT.

JOURNAL OF DIABETES INVESTIGATION (2021)

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Review Physiology

The Effect of Inflammation on Bone

Scott Epsley et al.

Summary: Bone remodeling is a continual process involving osteoblasts and osteoclasts, where inflammation plays a crucial role in skewing the process towards resorption. Inflammatory mediators interact with bone cells to alter the expression of regulatory factors, leading to various bone-related pathologies. Further research is needed to advance early detection and treatments for bone diseases influenced by inflammation.

FRONTIERS IN PHYSIOLOGY (2021)

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Article Hematology

Defective palmitoylation of transferrin receptor triggers iron overload in Friedreich ataxia fibroblasts

Floriane Petit et al.

Summary: Friedreich ataxia (FRDA) is a genetic disease caused by a GAA repeat expansion in the FXN gene, leading to iron accumulation in the brain and heart of patients. Frataxin deficiency affects the palmitoylation of transferrin receptor 1 (TfR1). Treatments with artesunate, CoA, and dichloroacetate can improve TfR1 palmitoylation, reducing iron overload.

BLOOD (2021)

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Article Oncology

Proteogenomic and metabolomic characterization of human glioblastoma

Liang-Bo Wang et al.

Summary: Understanding the molecular pathogenesis of glioblastoma is crucial for improving diagnosis and treatment. Integrated analysis of genomic, proteomic, and metabolomic data on treatment-naive glioblastomas has identified key phosphorylation events and potential targets for specific tumor alterations. Immune subtypes with distinct immune cell types were discovered, and specific histone acetylation patterns were correlated with these subtypes, providing insights for stratification of patients for more effective treatment.

CANCER CELL (2021)

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Review Biochemistry & Molecular Biology

Metabolic consequences of obesity and type 2 diabetes: Balancing genes and environment for personalized care

Nicolas J. Pillon et al.

Summary: This review focuses on the influence of genetic and environmental factors on metabolism and highlights the importance of personalized strategies for prevention, management, and care to improve health outcomes and reduce the impact of metabolic diseases.

CELL (2021)

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Article Cell Biology

The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity

Suzhen Chen et al.

Summary: The plant chemical hyperforin (HPF) is found to promote adipose tissue thermogenesis by stimulating AMPK and PGC-1α, with dihydrolipoamide S-acetyltransferase (Dlat) identified as a direct molecular target of HPF. Genetic association studies suggest a link between DLAT variation and obesity. HPF shows promise as a pharmacological approach to treating obesity by promoting energy expenditure.

CELL METABOLISM (2021)

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Article Multidisciplinary Sciences

Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line

Katharina Klose et al.

Summary: The study evaluated the independent and synergistic effects of metformin and DCA on canine prostate adenocarcinoma and transitional cell carcinoma cell lines, showing synergistic effects in both neoplastic cell lines and fibroblasts. Metformin uptake in tumor cells was measurable by quantitative HPLC.

PLOS ONE (2021)

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Article Medicine, General & Internal

Prognostic value of lactate levels and lactate clearance in sepsis and septic shock with initial hyperlactatemia A retrospective cohort study according to the Sepsis-3 definitions

Seong Geun Lee et al.

Summary: This study found that 6-hour lactate levels and lactate clearance can serve as important markers for predicting 30-day mortality in patients with sepsis and septic shock, with 6-hour lactate levels showing a higher predictive value compared to lactate clearance rates.

MEDICINE (2021)

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Review Multidisciplinary Sciences

Function and regulation of the divisome for mitochondrial fission

Felix Kraus et al.

Summary: Mitochondria form dynamic networks through fusion and fission events, with fission serving as an endpoint event in signaling axis for cells to sense and respond to external cues. The fission process is coordinated by membrane-associated adaptors, influenced by organellar and cytoskeletal interactions, and executed by the GTPase DRP1. Separating the functional and regulatory aspects of the 'mitochondrial divisome' into core and accessory machinery provides a mechanistic understanding of the mitochondrial fission process.

NATURE (2021)

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Article Multidisciplinary Sciences

Metabolic support of tumour-infiltrating regulatory T cells by lactic acid

McLane J. Watson et al.

Summary: T-reg cells exhibit broad heterogeneity in glucose metabolism within normal and transformed tissues, utilizing an alternative metabolic pathway to maintain their suppressive function and proliferation. Glucose uptake is correlated with poorer suppressive function and long-term instability, while high-glucose conditions impair T-reg cell function and stability. Additionally, T-reg cells upregulate pathways involved in the metabolism of lactic acid, with lactate uptake being dispensable for peripheral T-reg cells but required intratumorally for slowed tumor growth and increased response to immunotherapy.

NATURE (2021)

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Review Multidisciplinary Sciences

The spectrum of inflammatory responses

Ruslan Medzhitov

Summary: Inflammation plays a crucial role in maintaining homeostasis and structural integrity of tissues and organs in animals. Recent research has revealed a wide range of biological processes involving inflammatory control, urging for a new framework beyond its traditional roles in defense against infection and injury. New perspectives and research directions are discussed to address the current gaps in understanding inflammation biology.

SCIENCE (2021)

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Article Multidisciplinary Sciences

Screening of metabolic modulators identifies new strategies to target metabolic reprogramming in melanoma

Cecilie Abildgaard et al.

Summary: Metabolic modulation can be a potential therapeutic approach for melanoma, with two compounds enhancing the effect of the BRAF inhibitor. The combinations of these metabolic modulators led to increased production of reactive oxygen species, suggesting a role of oxidative stress in the cellular response. This study supports the use of such combination therapies in cancer treatment for metastatic melanoma patients.

SCIENTIFIC REPORTS (2021)

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Article Cell Biology

Integrative structure of a 10-megadalton eukaryotic pyruvate dehydrogenase complex from native cell extracts

Fotis L. Kyrilis et al.

Summary: The study successfully identified fully assembled pyruvate dehydrogenase complex in native cell extracts and characterized its structure using multiple techniques. The findings provide a framework for further understanding the structure and function of the complex.

CELL REPORTS (2021)

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Article Biology

Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction

Rabina Mainali et al.

Summary: Metabolic reprogramming occurs in the immune system during sepsis, particularly in the liver, with changes in lipid metabolism, mitochondrial energy, and redox balance. Targeting mitochondrial energy metabolism can rebalance the transcriptional and metabolic manifestations of sepsis in the liver.

ELIFE (2021)

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Article Endocrinology & Metabolism

Insulin resistance is mechanistically linked to hepatic mitochondrial remodeling in non-alcoholic fatty liver disease

Chris E. Shannon et al.

Summary: Insulin resistance and altered hepatic mitochondrial function are key features of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). This study found that insulin sensitization with pioglitazone can mitigate mitochondrial dysfunction in the liver, which is independent of changes in hepatic lipid accumulation. The research highlights potential therapeutic targets for T2D and NAFLD, emphasizing the benefits of insulin sensitization in managing obesity-related diseases.

MOLECULAR METABOLISM (2021)

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Review Cell Biology

The Role of Cytokines and Chemokines in Shaping the Immune Microenvironment of Glioblastoma: Implications for Immunotherapy

Erica C. F. Yeo et al.

Summary: Glioblastoma is the most common primary brain tumor in adults, with conventional treatments showing limited improvement in patient survival over the past decade. The immunosuppressive mechanisms employed by tumor cells can hinder treatment efficacy, highlighting the importance of understanding intercellular interactions for potential immunotherapeutic targeting and better patient outcomes.

CELLS (2021)

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Article Biochemistry & Molecular Biology

Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

Ester Gangoso et al.

Summary: In this study, it was found that GBM stem cells acquire the ability to evade immune clearance through epigenetic immunoediting, leading to the formation of an immunosuppressive tumor microenvironment. This process is not driven by genetic selection but by altering the transcriptional and epigenetic profile of GSCs after immune attack.

CELL (2021)

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Review Biochemistry & Molecular Biology

Mechanisms and disease consequences of nonalcoholic fatty liver disease

Rohit Loomba et al.

Summary: NAFLD and NASH are leading chronic liver diseases worldwide, causing progressive liver injury that can lead to cirrhosis and hepatocellular carcinoma. These diseases are associated with hepatic glucose and lipid metabolism, and are influenced by genetic, epigenetic, and environmental factors.

CELL (2021)

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Article Pharmacology & Pharmacy

Pharmacokinetic and Biochemical Profiling of Sodium Dichloroacetate in Pregnant Ewes and Fetuses

Serene Joseph et al.

Summary: The study showed that sodium dichloroacetate (DCA) can cross the placental barrier to reach the fetal circulation and reduce fetal lactate concentrations. Pharmacokinetic modeling indicated that DCA inhibits lactate production in both fetal and maternal compartments. Furthermore, DCA exposure led to decreased expression of glutathione transferase zetal in ewes and their fetuses, resulting in reduced DCA metabolism.

DRUG METABOLISM AND DISPOSITION (2021)

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Article Multidisciplinary Sciences

REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity

Guolian Ding et al.

Summary: The nuclear receptors REV-ERB-alpha and REV-ERB-beta in GABAergic neurons control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production, peaking at waking. This mechanism is crucial for understanding the extended dawn phenomenon in type 2 diabetes.

NATURE (2021)

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Article Multidisciplinary Sciences

Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence

Sekyu Choi et al.

Summary: The study revealed that corticosterone regulates hair follicle stem cell (HFSC) quiescence and hair growth in mice, with chronic stress prolonging HFSC quiescence and maintaining hair follicles in an extended resting phase. The mechanism involves corticosterone suppressing the expression of Gas6 gene through acting on dermal papillae, and restoring Gas6 expression can overcome stress-induced inhibition of HFSC activation and hair growth.

NATURE (2021)

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Article Multidisciplinary Sciences

Landmarks of human embryonic development inscribed in somatic mutations

Sara Bizzotto et al.

Summary: Through high-depth whole-genome sequencing and single-cell analysis, this study reveals the process of early cell division in human embryonic development and explores the asymmetric contributions of early progenitors to the formation of different organs and tissues.

SCIENCE (2021)

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Article Cell Biology

FoxO1 inhibition alleviates type 2 diabetes-related diastolic dysfunction by increasing myocardial pyruvate dehydrogenase activity

Keshav Gopal et al.

Summary: The study demonstrates that inhibition of FoxO1 improves diastolic dysfunction in diabetic cardiomyopathy by stimulating PDH activity. The interplay between FoxO1 inhibition and PDH activity plays a crucial role in improving cardiac function.

CELL REPORTS (2021)

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Article Oncology

Glycolysis and Fatty Acid Oxidation Inhibition Improves Survival in Glioblastoma

Kelly J. McKelvey et al.

Summary: Study found that dual targeting of glycolytic and FAO metabolic pathways is a potential treatment approach that can improve survival rates for GBM patients, warranting further research.

FRONTIERS IN ONCOLOGY (2021)

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Review Biochemistry & Molecular Biology

Targeting pyruvate dehydrogenase kinase signaling in the development of effective cancer therapy

Saleha Anwar et al.

Summary: The metabolism of cancer cells is closely related to the inhibition of PDC, which can be targeted as an attractive strategy in anticancer therapy. Research on the PDC/PDK axis may contribute to the therapeutic management of cancer by developing potential small-molecule PDK inhibitors. In recent years, there has been increasing attention from the scientific community in targeting the PDC/PDK axis for cancer treatment.

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER (2021)

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Article Cell Biology

The requirement for pyruvate dehydrogenase in leukemogenesis depends on cell lineage

Sojeong Jun et al.

Summary: Cancer cells have metabolic similarities with normal tissues, but differences may be due to reprogramming during transformation or maintenance of specific cell type metabolism. This study compared glucose metabolism in hematopoiesis and leukemia, finding that PDH deletion affects the development of T cell leukemia but not myeloid neoplasms, emphasizing the role of PDH in maintaining normal cell metabolism in leukemia.

CELL METABOLISM (2021)

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Article Cell Biology

Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2

Moritz Reiterer et al.

Summary: The study found that hyperglycemia is common among patients with ARDS, and in patients with both ARDS and COVID-19, insulin resistance is the main cause of hyperglycemia. COVID-19 patients have lower levels of adiponectin, and SARS-CoV-2 may infect adipocytes, leading to dysfunction of adipose tissue.

CELL METABOLISM (2021)

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Review Biochemistry & Molecular Biology

Targeting Glucose Metabolism of Cancer Cells with Dichloroacetate to Radiosensitize High-Grade Gliomas

Kristina M. Cook et al.

Summary: Radioresistance in high-grade gliomas is mainly driven by altered metabolism and hypoxia, with glucose metabolism being a key factor. Novel strategies to improve radiosensitivity include the use of metabolic drugs like dichloroacetate (DCA), which target the Warburg effect and enhance mitochondrial oxidative phosphorylation to overcome radioresistance. Recent studies have shown promising results in pre-clinical and clinical settings, suggesting DCA could be an effective radiosensitizer for HGG patients.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Biochemistry & Molecular Biology

Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1

Tae Suk Kim et al.

Summary: This study demonstrates the anticancer effects of the combination treatment of metformin and DCA on liver cancer cells, including induction of apoptosis, inhibition of mTOR complex I signaling through upregulated AMPK-independent pathway, and increased reactive oxygen species levels in cancer cells. Moreover, the combination treatment did not affect the viability of normal hepatocytes, suggesting its broad applicability.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Multidisciplinary Sciences

Obesity accelerates hair thinning by stem cell-centric converging mechanisms

Hironobu Morinaga et al.

Summary: Obesity-induced stress accelerates hair thinning by targeting HFSCs, suppressing stem cell inflammatory signals and inhibiting organ regeneration signals.

NATURE (2021)

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Article Multidisciplinary Sciences

A Warburg-like metabolic program coordinates Wnt, AMPK, and mTOR signaling pathways in epileptogenesis

Roaya S. Alqurashi et al.

Summary: This study identified a transient program of molecular and metabolic signaling in the early epileptogenic period, with a focus on Wnt signaling, metabolic reprogramming, and mTOR activation. The newly discovered molecular mechanism may provide insights for refining therapeutic strategies and attenuating recurrent seizures in epilepsy.

PLOS ONE (2021)

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Article Virology

Metabolic shifts modulate lung injury caused by infection with H1N1 influenza A virus

Katherine E. Nolan et al.

Summary: This study found that inhibiting glycolysis worsens outcomes of influenza infection, while promoting TCA cycle flux and inhibiting OXPHOS can mitigate the effects of the virus. These findings suggest that a shift to glycolysis may be host-protective in influenza.

VIROLOGY (2021)

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Article Cell Biology

Sirtuin 3 regulates mitochondrial protein acetylation and metabolism in tubular epithelial cells during renal fibrosis

Yu Zhang et al.

Summary: Proximal tubular epithelial cells (TECs) require high energy and rely on mitochondrial oxidative phosphorylation as their main energy source. However, in renal fibrosis, this process is disrupted. Sirtuin 3 (SIRT3), a mitochondrial protein, regulates mitochondrial metabolic function through deacetylation. Decreased SIRT3 expression in TECs during early renal fibrosis leads to increased acetylation in mitochondria, contributing to the development of severe renal fibrosis.Activation of SIRT3 can prevent renal fibrosis by reducing acetylation levels in mitochondrial proteins.

CELL DEATH & DISEASE (2021)

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Article Multidisciplinary Sciences

Lactate and IL6 define separable paths of inflammatory metabolic adaptation

Stefanie Dichtl et al.

Summary: Lactate, a product of Warburg-type metabolism in inflammatory macrophages, has been shown to modify histones and promote gene expression related to tissue repair. The presence of IL6 and Arg1 is correlated with Kla, suggesting a metabolic rewiring in macrophages under inflammatory stress.

SCIENCE ADVANCES (2021)

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Article Oncology

Non-Canonical Role of PDK1 as a Negative Regulator of Apoptosis through Macromolecular Complexes Assembly at the ER-Mitochondria Interface in Oncogene-Driven NSCLC

Viviana De Rosa et al.

Summary: The downregulation of PDK1 enhances cancer cell respiration and promotes apoptosis, making tumors more susceptible to tyrosine kinase inhibitors. PDK1 also drives the formation of macromolecular complexes at the ER-mitochondria interface, indirectly anchoring anti-apoptotic proteins to the mitochondrial membrane.

CANCERS (2021)

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Article Biochemistry & Molecular Biology

Pyruvate Dehydrogenase Kinase Protects Dopaminergic Neurons from Oxidative Stress in Drosophila DJ-1 Null Mutants

Yoonjeong Lee et al.

Summary: DJ-1 is a causative gene of early-onset familial Parkinson's disease (PD), and it influences the pathogenesis of sporadic PD by affecting reactive oxygen species (ROS) levels. PDK and PDP have been shown to play critical roles in protecting against oxidative stress by regulating glucose metabolism in the mitochondria, which is a major source of intracellular ROS.

MOLECULES AND CELLS (2021)

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Review Endocrinology & Metabolism

The metabolic roots of senescence: mechanisms and opportunities for intervention

Christopher D. Wiley et al.

Summary: Cellular senescence involves a permanent proliferative arrest and the release of biologically active molecules known as SASP. Studies show that senescence and SASP are sensitive to metabolic states, potentially driving phenotypes associated with metabolic dysfunction. Effective interventions may disrupt the feedback loop in which cellular senescence promotes metabolic diseases.

NATURE METABOLISM (2021)

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Article Oncology

LncRNA MEG3 promotes endoplasmic reticulum stress and suppresses proliferation and invasion of colorectal carcinoma cells through the MEG3/miR-103a-3p/PDHB ceRNA pathway

Guoqin Wang et al.

Summary: MEG3 functions as a suppressor in colorectal carcinoma by inhibiting malignancy and proliferation of cancer cells, inducing ER stress, and suppressing invasion; miR-103a-3p is a target of MEG3 and is also involved in targeting PDHB; the ceRNA pathway involving MEG3 may represent a novel mechanism in regulating colorectal carcinoma.

NEOPLASMA (2021)

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Review Chemistry, Medicinal

Pyruvate Dehydrogenase as a Therapeutic Target for Nonalcoholic Fatty Liver Disease

Christina T. Saed et al.

Summary: Excess caloric intake and a sedentary lifestyle in the general population have increased the prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). NAFLD poses risks such as insulin resistance, type 2 diabetes, and cardiovascular disease, with proposed multifactorial mechanisms including inflammation, oxidative stress, and mitochondrial dysfunction. Recent studies suggest that mitochondrial dysfunction in NAFLD may impair glucose oxidation, contributing to hepatic steatosis and glucose metabolism abnormalities.

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE (2021)

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Article Physiology

Reprogramming of aerobic glycolysis in non-transformed mouse liver with pyruvate dehydrogenase complex deficiency

Mulchand S. Patel et al.

Summary: The study reveals significant changes in gene expression of key enzymes in the liver of PDC-deficient mice, showing characteristics of aerobic glycolysis. The mechanism(s) responsible for these changes appears distinct from that which induces the Warburg effect in some cancer cells.

PHYSIOLOGICAL REPORTS (2021)

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Article Environmental Sciences

Dichloroacetate attenuates the stemness of colorectal cancer cells via trigerring ferroptosis through sequestering iron in lysosomes

Jie Sun et al.

Summary: The study demonstrated that dichloroacetate (DCA) could reduce colorectal cancer cell stemness in a dose-dependent manner, and trigger ferroptosis in colorectal cancer stem cells, suggesting its potential as a therapeutic approach for targeting colorectal cancer stem cells.

ENVIRONMENTAL TOXICOLOGY (2021)

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Review Immunology

Lactate modulation of immune responses in inflammatory versus tumour microenvironments

Michelangelo Certo et al.

Summary: The microenvironments of cancerous tissues and tissues affected by chronic inflammatory diseases exhibit different immune states but similar metabolic states. Understanding the metabolic signature allows for therapeutic intervention to reset metabolite availability and correct dysregulated immune states.

NATURE REVIEWS IMMUNOLOGY (2021)

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Article Biochemistry & Molecular Biology

Bioenergetic deficits in Huntington's disease iPSC-derived neural cells and rescue with glycolytic metabolites

Amanda J. Kedaigle et al.

HUMAN MOLECULAR GENETICS (2020)

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Review Biochemistry & Molecular Biology

Mitochondria, metabolic control and microRNA: Advances in understanding amphibian freeze tolerance

Kenneth B. Storey et al.

BIOFACTORS (2020)

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Article Urology & Nephrology

Reduction of mitochondria and up regulation of pyruvate dehydrogenase kinase 4 of skeletal muscle in patients with chronic kidney disease

Chenqi Xu et al.

NEPHROLOGY (2020)

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Review Biochemistry & Molecular Biology

The Mitochondrion as an Emerging Therapeutic Target in Cancer

Katherine G. Roth et al.

TRENDS IN MOLECULAR MEDICINE (2020)

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Article Oncology

Targeting reduced mitochondrial DNA quantity as a therapeutic approach in pediatric high-grade gliomas

Han Shen et al.

NEURO-ONCOLOGY (2020)

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Review Oncology

Cancer stem cells and their unique role in metastatic spread

Teresa Bernadette Steinbichler et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Article Gastroenterology & Hepatology

HNF4 Regulates Fatty Acid Oxidation and Is Required for Renewal of Intestinal Stem Cells in Mice

Lei Chen et al.

GASTROENTEROLOGY (2020)

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Article Cell Biology

Long non-coding RNA LINC00243 promotes proliferation and glycolysis in non-small cell lung cancer cells by positively regulating PDK4 through sponging miR-507

Xuegang Feng et al.

MOLECULAR AND CELLULAR BIOCHEMISTRY (2020)

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Review Cell Biology

Molecular mechanisms and physiological importance of circadian rhythms

Alina Patke et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2020)

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Article Cell Biology

Effects of resveratrol, granulocyte-macrophage colony-stimulating factor or dichloroacetic acid in the culture media on embryonic development and pregnancy rates in aged mice

Jeong Yoon et al.

AGING-US (2020)

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Review Immunology

Hypoxia and Innate Immunity: Keeping Up with the HIFsters

Sean P. Colgan et al.

ANNUAL REVIEW OF IMMUNOLOGY, VOL 38 (2020)

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Review Biochemistry & Molecular Biology

Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention

Yunhua Peng et al.

ANTIOXIDANTS & REDOX SIGNALING (2020)

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Article Biochemistry & Molecular Biology

Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy

Yi Zhu et al.

APOPTOSIS (2020)

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Article Oncology

Targeting aerobic glycolysis by dichloroacetate improves Newcastle disease virus-mediated viro-immunotherapy in hepatocellular carcinoma

Gang Meng et al.

BRITISH JOURNAL OF CANCER (2020)

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Article Oncology

Acidosis-induced metabolic reprogramming in tumor cells enhances the anti-proliferative activity of the PDK inhibitor dichloroacetate

C. A. Schoonjans et al.

CANCER LETTERS (2020)

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Article Cell Biology

Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier

Claire L. Bensard et al.

CELL METABOLISM (2020)

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Article Cardiac & Cardiovascular Systems

Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI

Oliver J. Rider et al.

CIRCULATION RESEARCH (2020)

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Article Biochemistry & Molecular Biology

Metabolic switch and epithelial-mesenchymal transition cooperate to regulate pluripotency

Hao Sun et al.

EMBO JOURNAL (2020)

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Review Biochemistry & Molecular Biology

Hypoxia-inducible factors in metabolic reprogramming during sepsis

Tineke Vanderhaeghen et al.

FEBS JOURNAL (2020)

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Article Gastroenterology & Hepatology

Mitochondrial impairment drives intestinal stem cell transition into dysfunctional Paneth cells predicting Crohn's disease recurrence

Sevana Khaloian et al.

GUT (2020)

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Article Biochemistry & Molecular Biology

Hepatic HAX-1 inactivation prevents metabolic diseases by enhancing mitochondrial activity and bile salt export

Fawzi Alogaili et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2020)

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Article Cell Biology

Stimulating pyruvate dehydrogenase complex reduces itaconate levels and enhances TCA cycle anabolic bioenergetics in acutely inflamed monocytes

Xuewei Zhu et al.

JOURNAL OF LEUKOCYTE BIOLOGY (2020)

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Article Multidisciplinary Sciences

Isolation of an archaeon at the prokaryote-eukaryote interface

Hiroyuki Imachi et al.

NATURE (2020)

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Review Pharmacology & Pharmacy

Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update

Robert Roskoski

PHARMACOLOGICAL RESEARCH (2020)

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Review Pharmacology & Pharmacy

Lactate/GPR81 signaling and proton motive force in cancer: Role in angiogenesis, immune escape, nutrition, and Warburg phenomenon

Timothy P. Brown et al.

PHARMACOLOGY & THERAPEUTICS (2020)

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Article Multidisciplinary Sciences

Imaging breast cancer using hyperpolarized carbon-13 MRI

Ferdia A. Gallagher et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Pharmacology & Pharmacy

Mice deficient in pyruvate dehydrogenase kinase 4 are protected against acetaminophen-induced hepatotoxicity

Luqi Duan et al.

TOXICOLOGY AND APPLIED PHARMACOLOGY (2020)

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Article Multidisciplinary Sciences

Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase

Erika M. Palmieri et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

Functional Consequences of PDK4 Deficiency in Doberman Pinscher Fibroblasts

Luiz Bolfer et al.

SCIENTIFIC REPORTS (2020)

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Article Cell Biology

Defective Mitochondrial Pyruvate Flux Affects Cell Bioenergetics in Alzheimer's Disease-Related Models

Alice Rossi et al.

CELL REPORTS (2020)

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Article Biochemistry & Molecular Biology

Nuclear accumulation of pyruvate dehydrogenase alpha 1 promotes histone acetylation and is essential for zygotic genome activation in porcine embryos

Wenjun Zhou et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2020)

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Article Oncology

Ascites-derived ALDH+CD44+tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer

Jiang Yu-Xin et al.

BRITISH JOURNAL OF CANCER (2020)

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Review Biochemistry & Molecular Biology

The Biology of Physiological Health

Janelle S. Ayres

CELL (2020)

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Editorial Material Cell Biology

Why Warburg Works: Lactate Controls Immune Evasion through GPR81

Kathrine Lundo et al.

CELL METABOLISM (2020)

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Article Cell Biology

Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

Leena P. Bharath et al.

CELL METABOLISM (2020)

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Article Cardiac & Cardiovascular Systems

Epigenetic Metabolic Reprogramming of Right Ventricular Fibroblasts in Pulmonary Arterial Hypertension A Pyruvate Dehydrogenase Kinase-Dependent Shift in Mitochondrial Metabolism Promotes Right Ventricular Fibrosis

Lian Tian et al.

CIRCULATION RESEARCH (2020)

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Review Respiratory System

Thiamine (vitamin B1) in septic shock: a targeted therapy

Ari Moskowitz et al.

JOURNAL OF THORACIC DISEASE (2020)

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Review Immunology

Crosstalk Between Hypoxia and ER Stress Response: A Key Regulator of Macrophage Polarization

Paula Diaz-Bulnes et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Multidisciplinary Sciences

T cells with dysfunctional mitochondria induce multimorbidity and premature senescence

Gabriela Desdin-Mico et al.

SCIENCE (2020)

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Article Genetics & Heredity

Synovial fibroblast-derived exosomal microRNA-106b suppresses chondrocyte proliferation and migration in rheumatoid arthritis via down-regulation of PDK4

Dan Liu et al.

JOURNAL OF MOLECULAR MEDICINE-JMM (2020)

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Article Multidisciplinary Sciences

Subpopulation targeting of pyruvate dehydrogenase and GLUT1 decouples metabolic heterogeneity during collective cancer cell invasion

R. Commander et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

N6-methyladenosine regulates glycolysis of cancer cells through PDK4

Zihan Li et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

Increasing carbohydrate oxidation improves contractile reserves and prevents hypertrophy in porcine right heart failure

Nikolaj Bogh et al.

SCIENTIFIC REPORTS (2020)

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Article Urology & Nephrology

Tuberous sclerosis 1 (Tsc1) mediated mTORC1 activation promotes glycolysis in tubular epithelial cells in kidney fibrosis

Hongdi Cao et al.

KIDNEY INTERNATIONAL (2020)

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Article Biochemistry & Molecular Biology

Frataxin-deficient cardiomyocytes present an altered thiol-redox state which targets actin and pyruvate dehydrogenase

Rosa Purroy et al.

REDOX BIOLOGY (2020)

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Article Biochemistry & Molecular Biology

Acetyl-CoA Derived from Hepatic Peroxisomal β-Oxidation Inhibits Autophagy and Promotes Steatosis via mTORC1 Activation

Anyuan He et al.

MOLECULAR CELL (2020)

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Article Biochemistry & Molecular Biology

STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer

Monika Oberhuber et al.

MOLECULAR SYSTEMS BIOLOGY (2020)

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Article Multidisciplinary Sciences

Hepatic NADH reductive stress underlies common variation in metabolic traits

Russell P. Goodman et al.

NATURE (2020)

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Article Multidisciplinary Sciences

poly(UG)-tailed RNAs in genome protection and epigenetic inheritance

Aditi Shukla et al.

NATURE (2020)

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Article Cell Biology

The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan

Kelvin Yen et al.

AGING-US (2020)

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Article Urology & Nephrology

Skeletal Muscle Mitochondrial Dysfunction Is Present in Patients with CKD before Initiation of Maintenance Hemodialysis

Jorge L. Gamboa et al.

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2020)

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Review Cell Biology

Mitochondrial Metabolism as a Target for Cancer Therapy

Karthik Vasan et al.

CELL METABOLISM (2020)

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Review Biochemistry & Molecular Biology

Mitochondria dysfunction and metabolic reprogramming as drivers of idiopathic pulmonary fibrosis

Marta Bueno et al.

REDOX BIOLOGY (2020)

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Article Multidisciplinary Sciences

NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level

Di Zhu et al.

SCIENCE ADVANCES (2020)

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Article Multidisciplinary Sciences

Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics

Ana Victoria Lechuga-Vieco et al.

SCIENCE ADVANCES (2020)

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Article Biochemistry & Molecular Biology

Cardiolipin-deficient cells have decreased levels of the iron-sulfur biogenesis protein frataxin

Yiran Li et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2020)

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Review Cell Biology

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

Allison K. Meyers et al.

CELLS (2020)

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Article Biochemistry & Molecular Biology

Ethyl pyruvate protects against sepsis-associated encephalopathy through inhibiting the NLRP3 inflammasome

Xiaoli Zhong et al.

MOLECULAR MEDICINE (2020)

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Article Biochemistry & Molecular Biology

Lactate Elicits ER-Mitochondrial Mg2+ Dynamics to Integrate Cellular Metabolism

Cassidy C. Daw et al.

CELL (2020)

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Review Biotechnology & Applied Microbiology

Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing

Stephen C. Cunnane et al.

NATURE REVIEWS DRUG DISCOVERY (2020)

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Article Anesthesiology

Mitochondrial bioenergetics, glial reactivity, and pain-related behavior can be restored by dichloroacetate treatment in rodent pain models

Valentina Lagos-Rodriguez et al.

PAIN (2020)

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Article Endocrinology & Metabolism

Insulin resistance induced by growth hormone is linked to lipolysis and associated with suppressed pyruvate dehydrogenase activity in skeletal muscle: a 2x2 factorial, randomised, crossover study in human individuals

Astrid J. Hjelholt et al.

DIABETOLOGIA (2020)

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Article Multidisciplinary Sciences

An essential role for cardiolipin in the stability and function of the mitochondrial calcium uniporter

Sagnika Ghosh et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Review Neurosciences

Neuronal and astroglial monocarboxylate transporters play key but distinct roles in hippocampus-dependent learning and memory formation

Citlalli Netzahualcoyotzi et al.

PROGRESS IN NEUROBIOLOGY (2020)

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Article Multidisciplinary Sciences

The hepatocyte clock and feeding control chronophysiology of multiple liver cell types

Dongyin Guan et al.

SCIENCE (2020)

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Article Biochemistry & Molecular Biology

Time-restricted feeding alleviates cardiac dysfunction induced by simulated microgravity via restoring cardiac FGF21 signaling

Xin-Pei Wang et al.

FASEB JOURNAL (2020)

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Review Endocrinology & Metabolism

Metabolic Implications of Circadian-HIF Crosstalk

Clara B. Peek

TRENDS IN ENDOCRINOLOGY AND METABOLISM (2020)

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Article Biochemistry & Molecular Biology

Overexpression of pyruvate dehydrogenase phosphatase 1 promotes the progression of pancreatic adenocarcinoma by regulating energy-related AMPK/mTOR signaling

Ye Li et al.

CELL AND BIOSCIENCE (2020)

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Review Medicine, Research & Experimental

Hypoxia-inducible factors and diabetes

Jenny E. Gunton

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Review Medicine, Research & Experimental

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Ellen C. de Heer et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Article Genetics & Heredity

Pyruvate dehydrogenase kinase/lactate axis: a therapeutic target for neovascular age-related macular degeneration identified by metabolomics

Vincent Lambert et al.

JOURNAL OF MOLECULAR MEDICINE-JMM (2020)

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Article Biochemistry & Molecular Biology

Phosphorylation of PDHA by AMPK Drives TCA Cycle to Promote Cancer Metastasis

Zhen Cai et al.

MOLECULAR CELL (2020)

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Article Medicine, General & Internal

Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis

Sabrina Paganoni et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Pharmacology & Pharmacy

Distal control of mitochondrial biogenesis and respiratory activity by extracellular lactate caused by large-scale deletion of mitochondrial DNA

Emi Ogasawara et al.

PHARMACOLOGICAL RESEARCH (2020)

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Article Multidisciplinary Sciences

mTOR-mediated cancer drug resistance suppresses autophagy and generates a druggable metabolic vulnerability

Niklas Gremke et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

TGF-β1 is a regulator of the pyruvate dehydrogenase complex in fibroblasts

Edward R. Smith et al.

SCIENTIFIC REPORTS (2020)

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Article Cell Biology

Lactate Dehydrogenase A Governs Cardiac Hypertrophic Growth in Response to Hemodynamic Stress

Chongshan Dai et al.

CELL REPORTS (2020)

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Article Biology

Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria

Sara M. Nowinski et al.

ELIFE (2020)

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Editorial Material Multidisciplinary Sciences

Prehistoric Hibernation

M. R. Whitney et al.

AMERICAN SCIENTIST (2020)

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Review Biochemistry & Molecular Biology

Principles of Self-Organization of the Mammalian Embryo

Meng Zhu et al.

CELL (2020)

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Article Immunology

Role of glucose metabolism in aggressive phenotype of fibroblast-like synoviocytes: Latest evidence and therapeutic approaches in rheumatoid arthritis

Maryam Masoumi et al.

INTERNATIONAL IMMUNOPHARMACOLOGY (2020)

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Article Biochemistry & Molecular Biology

Dichloroacetate Radiosensitizes Hypoxic Breast Cancer Cells

Sven de Mey et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Multidisciplinary Sciences

Fibrosis: from mechanisms to medicines

Neil C. Henderson et al.

NATURE (2020)

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Article Endocrinology & Metabolism

Nutritional modulation of heart failure in mitochondrial pyruvate carrier-deficient mice

Kyle S. McCommis et al.

NATURE METABOLISM (2020)

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Article Multidisciplinary Sciences

Dichloroacetate-induced metabolic reprogramming improves lifespan in a Drosophila model of surviving sepsis

Veli Bakalov et al.

PLOS ONE (2020)

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Article Endocrinology & Metabolism

PDK2-enhanced glycolysis promotes fibroblast proliferation in thyroid-associated ophthalmopathy

Ruiqi Ma et al.

JOURNAL OF MOLECULAR ENDOCRINOLOGY (2020)

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Article Cell Biology

Pyruvate dehydrogenase kinase is a negative regulator of interleukin-10 production in macrophages

Yi Rang Na et al.

JOURNAL OF MOLECULAR CELL BIOLOGY (2020)

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Article Multidisciplinary Sciences

Comprehensive quantification of fuel use by the failing and nonfailing human heart

Danielle Murashige et al.

SCIENCE (2020)

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Review Biochemistry & Molecular Biology

Regulation of cancer cell metabolism: oncogenic MYC in the driver's seat

Yang Dong et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

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Article Gastroenterology & Hepatology

PDK4-Deficiency Reprograms Intrahepatic Glucose and Lipid Metabolism to Facilitate Liver Regeneration in Mice

Yulan Zhao et al.

HEPATOLOGY COMMUNICATIONS (2020)

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Article Endocrinology & Metabolism

Arousal-induced cortical activity triggers lactate release from astrocytes

Marc Zuend et al.

NATURE METABOLISM (2020)

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Article Endocrinology & Metabolism

Mitochondrial substrate utilization regulates cardiomyocyte cell-cycle progression

Alisson C. Cardoso et al.

NATURE METABOLISM (2020)

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Article Biology

Evidence of torpor in the tusks of Lystrosaurus from the Early Triassic of Antarctica

Megan R. Whitney et al.

COMMUNICATIONS BIOLOGY (2020)

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Article Physiology

Mitochondria in the Pulmonary Vasculature in Health and Disease: Oxygen-sensing, Metabolism, and Dynamics

Asish Dasgupta et al.

COMPREHENSIVE PHYSIOLOGY (2020)

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Review Oncology

Glioblastoma Stem cells: Driving Resilience through Chaos

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Targeting hepatic pyruvate dehydrogenase kinases restores insulin signaling and mitigates ChREBP-mediated lipogenesis in diet-induced obese mice

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The NAD+-Dependent SIRT1 Deacetylase Translates a Metabolic Switch into Regulatory Epigenetics in Skeletal Muscle Stem Cells

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CURRENT OPINION IN CELL BIOLOGY (2015)

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Increasing Pyruvate Dehydrogenase Flux as a Treatment for Diabetic Cardiomyopathy: A Combined C-13 Hyperpolarized Magnetic Resonance and Echocardiography Study

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Overexpression of pyruvate dehydrogenase kinase supports dichloroacetate as a candidate for cutaneous melanoma therapy

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Human Monocytes Undergo Functional Re-programming during Sepsis Mediated by Hypoxia-Inducible Factor-1α

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Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy

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PTH Promotes Bone Anabolism by Stimulating Aerobic Glycolysis via IGF Signaling

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Pyruvate Dehydrogenase Kinase 1 Participates in Macrophage Polarization via Regulating Glucose Metabolism

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Decreased mitochondrial bioenergetics and calcium buffering capacity in the basal ganglia correlates with motor deficits in a nonhuman primate model of aging

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Pyruvate prevents the development of age-dependent cognitive deficits in a mouse model of Alzheimer's disease without reducing amyloid and tau pathology

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Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency

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Neural Stem Cells in the Adult Subventricular Zone Oxidize Fatty Acids to Produce Energy and Support Neurogenic Activity

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Pyruvate Dehydrogenase Kinases: Therapeutic Targets for Diabetes and Cancers

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Elucidation of the Interaction Loci of the Human Pyruvate Dehydrogenase Complex E2.E3BP Core with Pyruvate Dehydrogenase Kinase 1 and Kinase 2 by HID Exchange Mass Spectrometry and Nuclear Magnetic Resonance

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Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster

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Loss of HIF-1α impairs GLUT4 translocation and glucose uptake by the skeletal muscle cells

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Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes

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Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

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Methyl pyruvate rescues mitochondrial damage caused by SIGMAR1 mutation related to amyotrophic lateral sclerosis

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Dichloroacetate induces autophagy in colorectal cancer cells and tumours

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Dichloroacetate prevents restenosis in preclinical animal models of vessel injury

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Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral sclerosis shifts energy generation from oxidative phosphorylation to glycolysis

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Inhibiting Sperm Pyruvate Dehydrogenase Complex and Its E3 Subunit, Dihydrolipoamide Dehydrogenase Affects Fertilization in Syrian Hamsters

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Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

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OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin

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HIF1α Modulates Cell Fate Reprogramming Through Early Glycolytic Shift and Upregulation of PDK1-3 and PKM2

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Aggregation and morphology control enables multiple cases of high-efficiency polymer solar cells

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Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

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Metabolic and transcriptional profiling reveals pyruvate dehydrogenase kinase 4 as a mediator of epithelial-mesenchymal transition and drug resistance in tumor cells

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Review Biochemistry & Molecular Biology

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Combined Targeting of PDK1 and EGFR Triggers Regression of Glioblastoma by Reversing the Warburg Effect

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CANCER RESEARCH (2013)

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The Hallmarks of Aging

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Mitochondrial Regulation in Pluripotent Stem Cells

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Regulation of Glycolysis by Pdk Functions as a Metabolic Checkpoint for Cell Cycle Quiescence in Hematopoietic Stem Cells

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Review Cardiac & Cardiovascular Systems

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Sirt3 Regulates Metabolic Flexibility of Skeletal Muscle Through Reversible Enzymatic Deacetylation

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A new locus for X-linked dominant CharcotMarieTooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene

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Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity

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AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function

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Ethyl pyruvate ameliorates albuminuria and glomerular injury in the animal model of diabetic nephropathy

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SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome

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Correction Clinical Neurology

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High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio

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Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition

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Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis

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Central lactate metabolism suppresses food intake via the hypothalamic AMP kinase/malonyl-CoA signaling pathway

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Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells

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HUMAN REPRODUCTION UPDATE (2009)

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Review Medicine, Research & Experimental

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Article Biochemistry & Molecular Biology

The up-regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1α

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Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy

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Hypoxia-Inducible Factor 1α Induces Fibrosis and Insulin Resistance in White Adipose Tissue

Nils Halberg et al.

MOLECULAR AND CELLULAR BIOLOGY (2009)

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Article Endocrinology & Metabolism

AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells

Lyudmyla G. Glushakova et al.

MOLECULAR GENETICS AND METABOLISM (2009)

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Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

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Changes in Temperature Preferences and Energy Homeostasis in Dystroglycan Mutants

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RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis

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Article Rheumatology

Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice

Li Bian et al.

ARTHRITIS RESEARCH & THERAPY (2009)

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Transcriptional Regulation of Carbohydrate Metabolism in the Human Pathogen Candida albicans

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PLOS PATHOGENS (2009)

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Metabolic profiling of Parkinson's disease: evidence of biomarker from gene expression analysis and rapid neural network detection

Shiek S. S. J. Ahmed et al.

JOURNAL OF BIOMEDICAL SCIENCE (2009)

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Role of dichloroacetate in the treatment of genetic mitochondrial diseases

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ADVANCED DRUG DELIVERY REVIEWS (2008)

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Article Endocrinology & Metabolism

Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice

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AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM (2008)

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Tissue-specific pyruvate dehydrogenase complex deficiency causes cardiac hypertrophy and sudden death of weaned male mice

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AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY (2008)

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Editorial Material Cardiac & Cardiovascular Systems

PDC deletion: the way to a man's heart disease

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AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY (2008)

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Mammalian hibernation as a model of disuse osteoporosis: the effects of physical inactivity on bone metabolism, structure, and strength

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Dichloroacetate enhances performance and reduces blood lactate during maximal cycle exercise in chronic obstructive pulmonary disease

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Mitochondrial dysfunction in mouse trisomy 16 brain

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Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer

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SIRT1 regulates circadian clock gene expression through PER2 deacetylation

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Activities of respiratory chain complexes and pyruvate dehydrogenase in isolated muscle mitochondria in premature neonates

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AMPK phosphorylation of raptor mediates a metabolic checkpoint

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A combined therapeutic approach for pyruvate dehydrogenase deficiency using self-complementary adeno-associated virus serotype-specific vectors and dichloroacetate

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NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α

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Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate

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Letter Medicine, General & Internal

Clinical and serological profile of primary biliary cirrhosis in young and elderly patients

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QJM-AN INTERNATIONAL JOURNAL OF MEDICINE (2008)

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Structural Basis for Inactivation of the Human Pyruvate Dehydrogenase Complex by Phosphorylation: Role of Disordered Phosphorylation Loops

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Structures of the human pyruvate dehydrogenase complex cores: A highly conserved catalytic center with flexible N-terminal domains

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Pyruvate dehydrogenase complex deficiency caused by ubiquitination and proteasome-mediated degradation of the E1β subunit

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Stable expression of HIF-1α in tubular epithelial cells promotes interstitial fibrosis

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Metabolic changes in pregnancy

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Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice

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Identification of the circadian transcriptome in adult mouse skeletal muscle

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PdhR (pyruvate dehydrogenase complex regulator) controls the respiratory electron transport system in Escherichia coli

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Hypoxia-inducible factor 1α is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif

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Oxidative metabolism of pyruvate is required for meiotic maturation of murine oocytes in vivo

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Metabolic targeting of hypoxia and HIF1 in solid tumors can enhance cytotoxic chemotherapy

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Type 2 diabetes and the risk of Parkinson's disease

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Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells

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A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth

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Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer

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Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation

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The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes

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Disordered lipid metabolism and the pathogenesis of insulin resistance

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Nanog and transcriptional networks in embryonic stem cell pluripotency

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Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression

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Malonaldehyde acts as a mitochondrial toxin: Inhibitory effects on respiratory function and enzyme activities in isolated rat liver mitochondria

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Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children

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The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1α-dependent mechanism

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E1 enzyme of the pyruvate dehydrogenase complex in Corynebactetium glutamicum: Molecular analysis of the gene and phylogenetic aspects

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Regulation of blood glucose by hypothalamic pyruvate metabolism

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Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery induced weight loss

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Novelty of the pyruvate metabolic enzyme dihydrolipoamide dehydrogenase in spermatozoa - Correlation of its localization, tyrosine phosphorylation, and activity during sperm capacitation

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Pyruvate dehydrogenase phosphatase deficiency: Identification of the first mutation in two brothers and restoration of activity by protein complementation

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Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice

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Obesity and metabolic syndrome in circadian Clock mutant mice

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Pyruvate administered after severe hypoglycemia reduces neuronal death and cognitive impairment

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Low oocyte mitochondrial DNA content in ovarian insufficiency

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Elevated n-3 fatty acids in a high-fat diet attenuate the increase in PDH kinase activity but not PDH activity in human skeletal muscle

EA Turvey et al.

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Dichloroacetate therapy attenuates the blood lactate response to submaximal exercise in patients with defects in mitochondrial energy metabolism

GE Duncan et al.

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Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure

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Mice deficient in dihydrolipoamide dehydrogenase show increased vulnerability to MPTP, malonate and 3-nitropropionic acid neurotoxicity

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Lactate in solid malignant tumors: Potential basis of a metabolic classification in clinical oncology

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CURRENT MEDICINAL CHEMISTRY (2004)

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Neurodegenerative disorders associated with diabetes mellitus

M Ristow

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Biochemical and structural brain alterations in female mice with cerebral pyruvate dehydrogenase deficiency

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The E4F protein is required for mitotic progression during embryonic cell cycles

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Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes

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Metabolic rate and body temperature reduction during hibernation and daily torpor

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Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise

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Characterization of the isozymes of pyruvate dehydrogenase phosphatase: implications for the regulation of pyruvate dehydrogenase activity

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A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells

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Starvation and diabetes reduce the amount of pyruvate dehydrogenase phosphatase in rat heart and kidney

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Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo

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Statin-associated myopathy

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Reduced PDK4 expression associates with increased insulin sensitivity in postobese patients

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Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development

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Obesity is associated with macrophage accumulation in adipose tissue

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Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance

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Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development

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Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice

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Lactate induces insulin resistance in skeletal muscle by suppressing glycolysis and impairing insulin signaling

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Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis

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Coordinated transcription of key pathways in the mouse by the circadian clock

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Pharmacological stimulation of the cholinergic antiinflammatory pathway

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Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants - A case study of endosymbiotic gene transfer

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Heterogeneous distribution of pyruvate dehydrogenase in the matrix of mitochondria

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Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-α ligands, glucocorticoids, and insulin

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The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001)

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Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its effect on early embryonic development

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Lipoic acid improves survival in transgenic mouse models of Huntington's disease

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Impairment of pyruvate dehydrogenase activity by acetaldehyde

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Caveats when considering ketogenic diets for the treatment of pyruvate dehydrogenase complex deficiency

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Probing the mechanism of inactivation of human pyruvate dehydrogenase by phosphorylation of three sites

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Frataxin activates mitochondrial energy conversion and oxidative phosphorylation

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Primordial carbonylated iron-sulfur compounds and the synthesis of pyruvate

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HIF-1: mediator of physiological and pathophysiological responses to hypoxia

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Oxygen and placental development during the first trimester: Implications for the pathophysiology of pre-eclampsia

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Coagulation abnormalities in acute lung injury and sepsis

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Cortical dysfunction in non-demented Parkinson's disease patients -: A combined 31P-MRS and 18FDG-PET study

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The pyruvate dehydrogenase E1 alpha gene is testosterone and prolactin regulated in prostate epithelial cells

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