☆ 4.7 Review

Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

FRONTIERS IN ENDOCRINOLOGY (2023)

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Article Cell Biology

METTL14 promotes doxorubicin-induced cardiomyocyte ferroptosis by regulating the KCNQ1OT1-miR-7-5p-TFRC axis

Shaowei Zhuang et al.

Summary: This study found that DOX induces myocardial injury by promoting ferroptosis. DOX treatment upregulates METTL14, increasing the sponge KCNQ1OT1 for miR-7-5p and inhibiting its activity. The lack of miR-7-5p expression leads to increased iron uptake and lipid reactive oxygen species production, demonstrating DOX-induced ferroptosis in AC16 cells.

CELL BIOLOGY AND TOXICOLOGY (2023)

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Review Biochemistry & Molecular Biology

The blood-retina barrier in health and disease

Fionn O'Leary et al.

Summary: The blood-retina barrier (BRB) separates the systemic circulation from the retina, consisting of the inner blood-retina barrier (iBRB) and the outer blood-retina barrier (oBRB). The integrity of the BRB is crucial for maintaining the function and structural integrity of the retina. Tight junction proteins play a key role in the iBRB, and disruption of the BRB can lead to retinal diseases.

FEBS JOURNAL (2023)

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Article Gastroenterology & Hepatology

Intracellular labile iron is a key regulator of hepcidin expression and iron metabolism

Yanmeng Li et al.

Summary: Intracellular labile iron has a dual function in regulating iron metabolism, inducing hepcidin expression in hepatocytes and stimulating the expression of bone morphogenic protein 6 (BMP6) in liver sinusoidal endothelial cells (LSECs) through the secretion of TNF alpha by hepatocytes. TNF alpha blockade dysregulates iron metabolism during iron overload and TNF alpha administration reduces iron burden in Hfe knockout hemochromatosis mice. TNF alpha could be a potential therapeutic target for HFE-associated hemochromatosis.

HEPATOLOGY INTERNATIONAL (2023)

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Article Toxicology

PM2.5 induces autophagy-dependent ferroptosis by endoplasmic reticulum stress in SH-SY5Y cells

Can Can Guo et al.

Summary: Fine particulate matter (PM2.5) is a global environmental problem that poses a threat to public health. This study found that PM2.5 exposure induces a form of cell death called ferroptosis, which is characterized by iron-dependent lipid peroxidation. This could be associated with the elevation of iron content caused by NCOA4-mediated ferritin autophagy.

JOURNAL OF APPLIED TOXICOLOGY (2023)

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Article Biochemistry & Molecular Biology

Hyperlipidemia induces proinflammatory responses by activating STING pathway through IRE1α-XBP1 in retinal endothelial cells

Zheyao Wen et al.

Summary: Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus. Chronic hyperglycemia and hyperlipidemia lead to endothelial inflammation, but the detailed mechanisms are not fully understood. This study analyzed single cell RNA sequencing data and found that the STING pathway is highly expressed in mouse retinal vessels. Further experiments showed that STING and p-TBK1 protein levels were increased in retinal endothelial cells of mice fed with a high fat diet. In vitro experiments demonstrated that STING pathway activation was induced by ER stress and potentiated by IRE1 alpha-XBP1 signaling. These findings suggest that targeting the STING pathway may provide a therapeutic approach for treating DR and other microvascular complications.

JOURNAL OF NUTRITIONAL BIOCHEMISTRY (2023)

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Review Physiology

Iron and the Pathophysiology of Diabetes

Alexandria Harrison et al.

Summary: High iron levels are associated with an increased risk of developing type 2 diabetes mellitus. Iron influences insulin secretion, insulin resistance, and hepatic glucose production. It plays a central role in metabolic processes and regulation, affecting metabolic rates, gluconeogenesis, fuel preference, insulin action, and adipocyte phenotype. These effects are observed in various tissues involved in diabetes phenotypes, with adipocytes, beta cells, and the liver playing key roles. Understanding the molecular mechanisms behind these effects has implications for diabetes prevention and treatment, as well as the pathogenesis of other age-related, nutrition-related, and iron-related diseases.

ANNUAL REVIEW OF PHYSIOLOGY (2023)

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Article Plant Sciences

Dihydroartemisinin elicits immunogenic death through ferroptosis-triggered ER stress and DNA damage for lung cancer immunotherapy

Ning Han et al.

Summary: This study demonstrates that DHA can promote immunogenic cell death in lung cancer by inducing ferroptosis and increasing endoplasmic reticulum stress and DNA damage. These findings provide novel insights into the regulation of the immune microenvironment for cancer immunotherapy by Chinese medicine phytopharmaceuticals.

PHYTOMEDICINE (2023)

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Editorial Material Ophthalmology

Anti-Vascular Endothelial Growth Factor Therapy for Complications of Diabetic Retinopathy-From Treatment to Prevention?

Tien-En Tan et al.

JAMA OPHTHALMOLOGY (2023)

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Article Ophthalmology

Minimal effect of conditional ferroportin KO in the neural retina implicates ferrous iron in retinal iron overload and degeneration

Yingrui Liu et al.

Summary: Iron-induced oxidative stress can cause or worsen retinal degenerative diseases, and retinal iron overload has been observed in mouse disease models. This study used mice with retina-specific knockout of ferroportin to investigate the role of impaired iron export in retinal iron overload. The results suggest that impaired iron export alone is not sufficient to explain the retinal iron overload observed in these mice.

EXPERIMENTAL EYE RESEARCH (2022)

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Article Ophthalmology

The gut microbiota in retinal diseases

Marie-Agnes Bringer et al.

Summary: The gut microbiota is a complex ecosystem that coevolves dynamically with the host, playing a crucial role in maintaining the balance between health and disease. Imbalance in gut microbial communities, known as dysbiosis, has been associated with various inflammatory, metabolic diseases, and central nervous system disorders.

EXPERIMENTAL EYE RESEARCH (2022)

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Article Cell Biology

PKCβII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis

Hai-Liang Zhang et al.

Summary: Through CRISPR-Cas9 and kinase inhibitor screening, Zhang et al. found that PKC beta II phosphorylates and activates ACSL4 to enhance polyunsaturated fatty acid-containing lipid biosynthesis, thereby promoting accumulation of lipid peroxidation and ferroptosis.

NATURE CELL BIOLOGY (2022)

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Article Ophthalmology

Lactucaxanthin Regulates the Cascade of Retinal Oxidative Stress, Endoplasmic Reticulum Stress and Inflammatory Signaling in Diabetic Rats

Elavarasan Anitha Rani et al.

Summary: The study investigated the protective mechanism of lactucaxanthin against retinal angiogenesis in diabetic retinopathy. Results showed that lactucaxanthin reduced oxidative stress, ER stress, and inflammatory response in diabetic rats. While the study had limitations in sample size and treatment duration, it highlighted the potential of lactucaxanthin in treating diabetic complications, with further clinical studies needed for validation.

OCULAR IMMUNOLOGY AND INFLAMMATION (2022)

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Article Pharmacology & Pharmacy

Resveratrol protected acrolein-induced ferroptosis and insulin secretion dysfunction via ER-stress- related PERK pathway in MIN6 cells

Xinhao Zhang et al.

Summary: Acrolein, a common food and environmental pollutant, induces ferroptosis in pancreatic beta cells, leading to dysfunction. Endoplasmic reticulum stress plays a critical role in acrolein-induced ferroptosis. Resveratrol can alleviate ER stress and protect pancreatic cells from acrolein-induced damage.

TOXICOLOGY (2022)

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Article Ophthalmology

Conditional knockout of hephaestin in the neural retina disrupts retinal iron homeostasis

Kevin R. Zhang et al.

Summary: Iron accumulation is associated with degenerative retinal diseases, and Heph plays a crucial role in regulating iron homeostasis in the retina, potentially affecting iron levels and degeneration of retinal ganglion cells.

EXPERIMENTAL EYE RESEARCH (2022)

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Article Biochemistry & Molecular Biology

Elabela promotes the retinal angiogenesis by inhibiting ferroptosis during the vaso-obliteration phase in mouse oxygen-induced retinopathy model

Jianhui Wang et al.

Summary: This study investigated the therapeutic potential and safety of early Elabela intervention treatment for retinopathy of prematurity (ROP) using a mouse model. The results showed that Elabela intraperitoneal injection significantly reduced avascular retinal area and increased vascular density in phase 1 of ROP mice. Further investigation revealed that mitochondrion-dependent ferroptosis was involved in oxidative stress-mediated vascular protection loss in phase 1 of ROP. Additionally, it was demonstrated that Elabela could rescue mitochondria-dependent ferroptosis by mediating the xCT/GPX4 axis.

FASEB JOURNAL (2022)

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Article Cell Biology

A novel miR-338-3p/SLC1A5 axis reprograms retinal pigment epithelium to increases its resistance to high glucose-induced cell ferroptosis

Jing Zhou et al.

Summary: This study revealed the molecular mechanisms underlying oxidative stress-induced cell ferroptosis during the pathogenesis of diabetic retinopathy. Targeting the miR-338-3p/SLC1A5 axis can block high glucose-induced cell ferroptosis.

JOURNAL OF MOLECULAR HISTOLOGY (2022)

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Review Neurosciences

Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications

Todd McLaughlin et al.

Summary: The retina, as part of the central nervous system, has limited capacity for self-reparation and regeneration. Cumulative environmental stress, such as high-energy demands and rapid protein turnover, can disrupt cellular protein and metabolic homeostasis, leading to dysfunction and cell death of retinal neurons. The unfolded protein response (UPR) is a cellular stress response that attempts to restore protein homeostasis in the endoplasmic reticulum through various mechanisms. Recent research has also highlighted the role of the UPR in cellular metabolism and mitochondrial function in retinal neurons.

MOLECULAR NEURODEGENERATION (2022)

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Article Pharmacology & Pharmacy

IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα

Juan Liu et al.

Summary: This study found that IKKβ is constitutively activated in healthy individuals and knock-in mice, and its activation may play a role in maintaining homeostasis instead of causing inflammation. Inhibition of IKKβ can disrupt homeostasis, while activation of AMPK can rebuild homeostasis and reduce mortality induced by inflammation.

ACTA PHARMACEUTICA SINICA B (2022)

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Article Biotechnology & Applied Microbiology

Astragaloside-IV alleviates high glucose-induced ferroptosis in retinal pigment epithelial cells by disrupting the expression of miR-138-5p/Sirt1/Nrf2

Xuyuan Tang et al.

Summary: This study demonstrates that AS-IV can alleviate the damage to RPE cells in diabetic retinopathy. The protective effect of AS-IV is mediated through the regulation of the mir-138-5p/Sirt1/Nrf2 pathway, which enhances the cellular antioxidant capacity and alleviates ferroptosis, ultimately leading to decreased cell death and potentially inhibiting the pathological process of DR.

BIOENGINEERED (2022)

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Article Medicine, General & Internal

Variability of Grading DR Screening Images among Non-Trained Retina Specialists

Andrzej Grzybowski et al.

Summary: Poland lacks a widespread diabetic retinopathy (DR) screening program and trained graders. This study compared the performance of three retinal specialists with no additional DR grading training in assessing real-life screening images and their performance against IDx-DR. The results showed that the retina specialists had high grader variability and limited concordance with IDx-DR results.

JOURNAL OF CLINICAL MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Ocular Hypertension Results in Hypoxia within Glia and Neurons throughout the Visual Projection

Assraa Hassan Jassim et al.

Summary: This study induced ocular hypertension in mice using a novel method and examined the hypoxic conditions in the visual pathway. The research found that hypoxia primarily occurred in different types of cells after OHT, and continued hypoxia may have a negative impact on the progression of glaucoma.

ANTIOXIDANTS (2022)

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Review Neurosciences

Non-coding RNAs in the regulation of blood-brain barrier functions in central nervous system disorders

Ping Sun et al.

Summary: The blood-brain barrier (BBB) is crucial for controlling exchanges between blood and brain, with damage being a common feature of CNS disorders. Non-coding RNAs play an important regulatory role in these diseases, serving as potential diagnostic and prognostic markers.

FLUIDS AND BARRIERS OF THE CNS (2022)

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Review Biochemistry & Molecular Biology

Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications

Brent R. Stockwell

Summary: This review describes the key regulators of ferroptosis and provides an overview of metabolism, ROS biology, and iron biology. Additionally, it highlights the important concepts and unanswered questions in the field of ferroptosis. The future holds promise for further breakthroughs in understanding the mechanisms of ferroptosis and utilizing it for therapeutic purposes.

CELL (2022)

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Article Cell Biology

m6A modification of circSPECC1 suppresses RPE oxidative damage and maintains retinal homeostasis

Xue Chen et al.

Summary: In this study, downregulated expression of circSPECC1 in the retinal pigment epithelium (RPE) of AMD patients was observed. CircSPECC1 insufficiency in RPE cells led to oxidative stress-induced ferroptosis, depolarization, and irregular lipid metabolism. The export of circSPECC1 transcript depended on its N6-methyladenosine (m6A) modification and interaction with miR-145-5p. It was found that circSPECC1 played a crucial role in resisting oxidative stress injuries and maintaining lipid metabolism in RPE, suggesting its potential as a therapeutic option for atrophic retinopathies like AMD.

CELL REPORTS (2022)

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Review Immunology

Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases

Meini Chen et al.

Summary: Pyroptosis is a type of programmed cell death characterized by rapid plasma membrane disruption and release of pro-inflammatory mediators. Recent studies have shown its involvement in various ocular diseases. This review summarizes the role of pyroptosis in common ocular diseases and suggests that targeting pyroptosis signaling pathways could be a potential therapeutic strategy.

JOURNAL OF NEUROINFLAMMATION (2022)

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Review Cell Biology

Targeting Novel Regulated Cell Death: Pyroptosis, Necroptosis, and Ferroptosis in Diabetic Retinopathy

Sheng Gao et al.

Summary: This article summarizes the mechanisms of three types of regulated cell death (RCD) in diabetic retinopathy (DR) and analyzes the recent advances in the association between novel RCD forms and DR. These findings provide new insights into the underlying pathogenic mechanisms of DR and propose potential therapeutic strategies.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Review Oncology

Involvement of transient receptor potential channels in ocular diseases: a narrative review

Tian-Jing Yang et al.

Summary: This narrative review explores the expression and function of TRP channels in various eye diseases, highlighting the vital roles they play and suggesting future research directions. Further investigations are needed to understand the mechanisms by which TRP channels contribute to eye disease pathophysiology in animal models and patients, with potential for future drug development targeting TRP channels.

ANNALS OF TRANSLATIONAL MEDICINE (2022)

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Article Nutrition & Dietetics

Correlations Between Iron Status and Body Composition in Patients With Type 2 Diabetes Mellitus

Chen Zimiao et al.

Summary: This study reveals the association between iron metabolism and body composition in patients with type 2 diabetes mellitus (T2DM), showing that higher ferritin and iron concentrations are positively associated with higher visceral fat mass and A/G ratio.

FRONTIERS IN NUTRITION (2022)

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Review Pharmacology & Pharmacy

Treatment and prevention of pathological mitochondrial dysfunction in retinal degeneration and in photoreceptor injury

Walter H. Moos et al.

Summary: Pathological deterioration of mitochondrial function is increasingly linked with degenerative illnesses, including genetic diseases. Vision impairment due to mitochondrial dysfunction is common in ophthalmic disorders, and alpha-lipoyl-L-carnitine has potential in treating eye diseases.

BIOCHEMICAL PHARMACOLOGY (2022)

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Article Pharmacology & Pharmacy

Blueberry anthocyanins extract attenuated diabetic retinopathy by inhibiting endoplasmic reticulum stress via the miR-182/OGG1 axis

Chaoqun Wang et al.

Summary: Blueberry anthocyanin extract (BAE) significantly inhibits the progression of diabetic retinopathy (DR) through the molecular regulation of the miR-182/OGG1 axis and ROS/ERS pathway.

JOURNAL OF PHARMACOLOGICAL SCIENCES (2022)

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Article Cell Biology

lncRNA ZFAS1 Positively Facilitates Endothelial Ferroptosis via miR-7-5p/ACSL4 Axis in Diabetic Retinopathy

Yu Liu et al.

Summary: Accumulating evidence has suggested the significant role of long noncoding RNAs (lncRNA) in regulating ferroptosis. This study shows that the upregulation of lncRNA zinc finger antisense 1 (ZFAS1) in high glucose-cultured human retinal endothelial cells (hRECs) activates ferroptosis. ZFAS1 functions as a competing endogenous RNA that competitively binds with microRNA-7-5p (miR-7-5p) and modulates the expression of its downstream molecule acyl-CoA synthetase long-chain family member 4 (ACSL4).

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2022)

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Review Immunology

ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis

Dongdong Zheng et al.

Summary: Endothelial cells act as a physical barrier between the blood and vessel wall in the vascular system, playing a crucial role in maintaining intravascular homeostasis. Dysfunction or death of endothelial cells may lead to the progression of various diseases, mainly associated with oxidative stress.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Multidisciplinary Sciences

Iron regulatory protein (IRP)-mediated iron homeostasis is critical for neutrophil development and differentiation in the bone marrow

Michael Bonadonna et al.

Summary: Iron plays a crucial role in hemoglobin synthesis in red blood cells, but recent studies have shown that it also has a broader role in hematopoiesis and immune system formation. Iron availability is regulated by iron-regulatory protein 1 and IRP2, which are essential for neutrophil development and differentiation. This study reveals the previously unrecognized importance of IRPs and iron metabolism in the formation of the innate immune system.

SCIENCE ADVANCES (2022)

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Article Multidisciplinary Sciences

Plasma iron controls neutrophil production and function

Joe N. Frost et al.

Summary: Low plasma iron induced by hepcidin inhibits neutrophil production and alters their effector functions, while having no significant effect on other types of white blood cells. Antagonizing endogenous hepcidin can enhance neutrophil production during acute inflammation. These findings suggest that plasma iron plays a role in modulating the profile of innate immunity, with potential therapeutic implications.

SCIENCE ADVANCES (2022)

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Review Cell Biology

Cytochrome P450 1B1: A Key Regulator of Ocular Iron Homeostasis and Oxidative Stress

Yong-Seok Song et al.

Summary: Cytochrome P450 1B1 plays an important role in maintaining retinal iron homeostasis. By modulating iron levels, it influences oxidative stress and the development of ocular diseases.

CELLS (2022)

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Article Ophthalmology

TRIM46 aggravated high glucose-induced hyper permeability and inflammatory response in human retinal capillary endothelial cells by promoting IκBα ubiquitination

Hangqi Shen et al.

Summary: This study reveals that TRIM46 interacts with I kappa B alpha to activate the NF-kappa B signaling pathway, enhancing cell proliferation inhibition, hyper permeability, and the inflammatory response of HRCECs in a high glucose state.

EYE AND VISION (2022)

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Article Cell Biology

Ferrostatin-1 alleviates tissue and cell damage in diabetic retinopathy by improving the antioxidant capacity of the Xc--GPX4 system

Jingzhi Shao et al.

Summary: Ferroptosis plays an important role in diabetic retinopathy, and treatment can improve antioxidant capacity and alleviate tissue or cell damage.

CELL DEATH DISCOVERY (2022)

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Article Endocrinology & Metabolism

Multimorbidity Among Adult Outpatients With Type 1 Diabetes in Germany

Louisa van den Boom et al.

Summary: The aim of this cross-sectional retrospective study was to estimate the prevalence of different physical and psychiatric disorders as well as multimorbidity in outpatients with type 1 diabetes (T1D) in Germany. The study found that patients with T1D are often multimorbid, and the multimorbidity is associated with age, gender, and high HbA1c values.

JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY (2022)

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Review Ophthalmology

Lactoferrin and its nano-formulations in rare eye diseases

Jiya Singh et al.

Summary: Lactoferrin is a substance that can be used to treat eye diseases related to the retina, cornea, and optic nerve. Studies have found that lactoferrin acts not only as an iron-binding protein, but also as a carrier for drug delivery through the blood-retina barrier, and is involved in cell cycle control.

INDIAN JOURNAL OF OPHTHALMOLOGY (2022)

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Letter Hematology

Endoplasmic reticulum stress controls iron metabolism through TMPRSS6 repression and hepcidin mRNA stabilization by RNA-binding protein HuR

Audrey Belot et al.

HAEMATOLOGICA (2021)

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Article Ophthalmology

TIM2 modulates retinal iron levels and is involved in blood-retinal barrier breakdown

Andreia Valenca et al.

Summary: The study revealed the presence of TIM2 receptors in the mouse retina and showed that experimental TIM2 downregulation increased Scara5 expression, promoting retinal ferritin uptake and inducing iron overload. This led to ROS overproduction and VEGF overexpression, resulting in impaired endothelial transport, BRB breakdown, and retinal edema. These findings suggest that TIM2 could be a potential target to counteract retinopathy by modulating retinal iron homeostasis.

EXPERIMENTAL EYE RESEARCH (2021)

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Article Oncology

TRIM46 contributes to high glucose-induced ferroptosis and cell growth inhibition in human retinal capillary endothelial cells by facilitating GPX4 ubiquitination

Jingfa Zhang et al.

Summary: The increased permeability of retinal capillary endothelial cells is a key feature in the progression of diabetic retinopathy. Mechanistic insights into the involvement of TRIM46 and GPX4 in regulating ferroptosis of HRCECs provide potential therapeutic targets for the treatment of DR.

EXPERIMENTAL CELL RESEARCH (2021)

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Review Cell Biology

Ferroptosis: mechanisms, biology and role in disease

Xuejun Jiang et al.

Summary: Ferroptosis, as a form of regulated cell death driven by iron-dependent phospholipid peroxidation, has seen significant growth in research in recent years. Studies have focused on molecular mechanisms, regulation, and functions of ferroptosis, linking this cell death modality to various pathologies and proposing its roles in normal physiology and potential therapeutic targeting.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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Article Endocrinology & Metabolism

Role of ferroptosis in the process of diabetes-induced endothelial dysfunction

Er-Fei Luo et al.

Summary: Ferroptosis is involved in endothelial dysfunction caused by diabetes, with activation of the p53-xCT-GSH axis playing a crucial role in endothelial cell ferroptosis and dysfunction.

WORLD JOURNAL OF DIABETES (2021)

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Review Biology

Potential Effects of Nutraceuticals in Retinopathy of Prematurity

Jessica K. W. Tsang et al.

Summary: Retinopathy of prematurity (ROP) is the most common cause of childhood blindness, characterized by hypoxia-induced retinal neovascularization. Nutritional supplements for newborns may offer a non-invasive way to protect retinal vasculature and improve ROP management.

LIFE-BASEL (2021)

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Article Biochemistry & Molecular Biology

A role of PIEZO1 in iron metabolism in mice and humans

Shang Ma et al.

Summary: Iron overload can cause progressive organ damage and is associated with genetic factors affecting iron homeostasis. Certain individuals with hereditary disorders may develop iron overload, and some GOF PIEZO1 alleles are linked to iron imbalance. The study demonstrates the key role of PIEZO1 in macrophage phagocytic activity and iron metabolism, with a particular GOF PIEZO1 allele showing a strong association with increased plasma iron levels in individuals of African descent.

CELL (2021)

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Article Endocrinology & Metabolism

Rheb1 promotes glucose-stimulated insulin secretion in human and mouse β-cells by upregulating GLUT expression

Yan Yang et al.

Summary: The small GTPase Rheb1 plays a critical role in regulating glucose-stimulated insulin secretion in beta-cells, suggesting a potential new target for therapeutic treatment of diabetes.

METABOLISM-CLINICAL AND EXPERIMENTAL (2021)

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Article Food Science & Technology

Anti-Apoptotic Effect of Flavokawain A on Ochratoxin-A-Induced Endothelial Cell Injury by Attenuation of Oxidative Stress via PI3K/AKT-Mediated Nrf2 Signaling Cascade

Peramaiyan Rajendran et al.

Summary: The study demonstrated that flavokawain A (FKA) can protect against endothelial injury induced by ochratoxin A (OTA) through the Nrf2 pathway and inhibition of NF kappa B, while also activating antioxidative and antiapoptotic signaling to prevent oxidative stress damage to endothelial cells.

TOXINS (2021)

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Review Pharmacology & Pharmacy

Conbercept for Treatment of Neovascular Age-Related Macular Degeneration and Visual Impairment due to Diabetic Macular Edema or Pathologic Myopia Choroidal Neovascularization: A Systematic Review and Meta-Analysis

Pengxiang Zhou et al.

Summary: Conbercept is well-tolerated and effective in improving vision and fundus condition in patients with neovascular age-related macular degeneration and diabetic macular edema compared with laser photocoagulation, intravitreal triamcinolone acetonide, and placebo. Further large-sample and long-term studies are needed.

FRONTIERS IN PHARMACOLOGY (2021)

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Article Biotechnology & Applied Microbiology

Downregulation of Circular RNA PSEN1 ameliorates ferroptosis of the high glucose treated retinal pigment epithelial cells via miR-200b-3p/cofilin-2 axis

Zhaoliang Zhu et al.

Summary: The study demonstrates that knockdown of circ-PSEN1 can alleviate HG-induced ferroptosis in ARPE19 cells via the miR-200b-3p/CFL2 axis, providing a novel therapeutic strategy for the treatment of DR.

BIOENGINEERED (2021)

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Article Biochemistry & Molecular Biology

SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46-mediated HDAC1 degradation

Zihan Zhang et al.

Summary: Identification of a new breast cancer risk locus, SNP rs4971059, has revealed its role in enhancing TRIM46 expression and promoting breast cancer cell proliferation and chemoresistance. TRIM46 acts as a ubiquitin ligase that targets histone deacetylase HDAC1 for degradation, regulating genes crucial in DNA replication and repair. Overexpression of TRIM46 in breast carcinomas is associated with worse prognosis, suggesting it as a potential target for breast cancer intervention.

EMBO JOURNAL (2021)

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Article Oncology

Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer

Nazia Chaudhary et al.

Summary: Lipocalin 2 overexpression leads to resistance to 5-fluorouracil in colon cancer cells by inhibiting ferroptosis. Inhibiting Lipocalin 2 function with a monoclonal antibody reduces chemoresistance and tumor progression. Lipocalin 2 and xCT exhibit a positive correlation in human tumor samples.

INTERNATIONAL JOURNAL OF CANCER (2021)

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Article Endocrinology & Metabolism

Iron aggravates hepatic insulin resistance in the absence of inflammation in a novel db/db mouse model with iron overload

Sandro Altamura et al.

Summary: The study reveals that hepatic iron accumulation may exacerbate symptoms related to metabolic syndrome and type 2 diabetes. It suggests that iron depletion strategies in combination with anti-diabetic drugs could potentially improve insulin resistance and diabetic late complications.

MOLECULAR METABOLISM (2021)

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Review Cell Biology

Down the Iron Path: Mitochondrial Iron Homeostasis and Beyond

Jonathan Dietz et al.

Summary: Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent, where mitochondria import iron to form clusters and heme, and supply the cell with heme for essential functions. Impairment in iron homeostasis can lead to various human diseases. Iron is stored and trafficked through carefully orchestrated processes intracellularly and within mitochondria.

CELLS (2021)

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Article Biochemistry & Molecular Biology

The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis

Cecilia Hognon et al.

Summary: The balance of iron homeostasis is crucial for maintaining cellular functions, and its dysregulation can lead to severe pathologies. The interaction with mRNA and conformational transitions are regulated by the iron-sensitive conformational equilibrium between cytosolic aconitase and IRP1, mediated by the presence of an iron-sulfur cluster. The role of the iron-sulfur cluster in driving the conformational transition is assessed through enhanced sampling molecular dynamics simulations.

BIOMOLECULES (2021)

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Article Biochemistry & Molecular Biology

Ferroptosis drives photoreceptor degeneration in mice with defects in all-trans-retinal clearance

Chao Chen et al.

Summary: The study reveals that the overload of atRAL leads to photoreceptor degeneration through activating ferroptosis. Inhibiting Fe2+ or lipid peroxidation can protect photoreceptor cells from ferroptosis induced by atRAL. Ferroptosis may be an important pathway of photoreceptor cell death in dry AMD and STGD1, and should be explored as a novel target for protection.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Review Physiology

FREE FATTY ACID RECEPTORS IN HEALTH AND DISEASE

Ikuo Kimura et al.

PHYSIOLOGICAL REVIEWS (2020)

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Review Cell Biology

Mitochondria as multifaceted regulators of cell death

Florian J. Bock et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2020)

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Article Endocrinology & Metabolism

Dietary Nonheme, Heme, and Total Iron Intake and the Risk of Diabetes in Adults: Results From the China Health and Nutrition Survey

Jingjing He et al.

DIABETES CARE (2020)

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Article Biochemistry & Molecular Biology

Protective effect of Liraglutide on diabetic retinal neurodegeneration via inhibiting oxidative stress and endoplasmic reticulum stress

Junli Liu et al.

NEUROCHEMISTRY INTERNATIONAL (2020)

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Review Cell Biology

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CELL DEATH & DISEASE (2020)

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Review Endocrinology & Metabolism

Iron metabolism and type 2 diabetes mellitus: A meta-analysis and systematic review

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Knockdown of MALAT1 attenuates high-glucose-induced angiogenesis and inflammation via endoplasmic reticulum stress in human retinal vascular endothelial cells

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SIRT3 deficiency is resistant to autophagy-dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels

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Ferrous but not ferric iron sulfate kills photoreceptors and induces photoreceptor -dependent RPE autofluorescence

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Emerging roles of non-coding RNAs in retinal diseases: A review

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Destruction of the blood-retina barrier in diabetic retinopathy depends on angiotensin-converting enzyme-mediated TGF-β1/Smad signaling pathway activation

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INTERNATIONAL IMMUNOPHARMACOLOGY (2020)

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Review Immunology

Recent advances in the NEK7-licensed NLRP3 inflammasome activation: Mechanisms, role in diseases and related inhibitors

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JOURNAL OF AUTOIMMUNITY (2020)

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MOLECULAR ASPECTS OF MEDICINE (2020)

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The role of reactive oxygen species in the pathogenesis and treatment of retinal diseases

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Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial

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Characterization of Retinal Microvascular Complications and the Effects of Endoplasmic Reticulum Stress in Mouse Models of Diabetic Atherosclerosis

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Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling

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Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases

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Auranofin Mediates Mitochondrial Dysregulation and Inflammatory Cell Death in Human Retinal Pigment Epithelial Cells: Implications of Retinal Neurodegenerative Diseases

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Retinopathy and RAAS Activation: Results From the Canadian Study of Longevity in Type 1 Diabetes

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Cyp1b1-deficient retinal astrocytes are more proliferative and migratory and are protected from oxidative stress and inflammation

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Correction Endocrinology & Metabolism

Dietary antioxidative supplements and diabetic retinopathy; a systematic review (10.1007/s40200-019-00434-x, 2019 )

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Global aetiology and epidemiology of type 2 diabetes mellitus and its complications

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Expression of genes associated with inflammation and iron metabolism in 3T3-L1 cells induced with macrophages-conditioned medium, glucose and iron

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Vascular endothelium dysfunction: a conservative target in metabolic disorders

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Review Nutrition & Dietetics

The Multiple Faces of the Metal Transporter ZIP14 (SLC39A14)

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Ellagic Acid Alleviates Hepatic Oxidative Stress and Insulin Resistance in Diabetic Female Rats

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Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression

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Prion protein modulates glucose homeostasis by altering intracellular iron

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Modeling the effects of lipid peroxidation during ferroptosis on membrane properties

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SCIENTIFIC REPORTS (2018)

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Five-Year Outcomes of Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy A Randomized Clinical Trial

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JAMA OPHTHALMOLOGY (2018)

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Changes of Cell Biochemical States Are Revealed in Protein Homomeric Complex Dynamics

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CELL (2018)

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Choroidal microvascular proliferation secondary to diabetes mellitus

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ONCOTARGET (2017)

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Correction Multidisciplinary Sciences

L-Ferritin Binding to Scara5: A New Iron Traffic Pathway Potentially Implicated in Retinopathy (vol 9, e106974, 2014)

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Conditional Muller Cell Ablation Leads to Retinal Iron Accumulation

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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2017)

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Role of free fatty acids in endothelial dysfunction

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IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040

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Review Biochemistry & Molecular Biology

Cellular iron uptake, trafficking and metabolism: Key molecules and mechanisms and their roles in disease

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2015)

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Review Endocrinology & Metabolism

Mechanisms Linking Glucose Homeostasis and Iron Metabolism Toward the Onset and Progression of Type 2 Diabetes

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Article Biochemistry & Molecular Biology

Cytosolic aconitase activity sustains adipogenic capacity of adipose tissue connecting iron metabolism and adipogenesis

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FASEB JOURNAL (2015)

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Article Medicine, Research & Experimental

Adipocyte iron regulates leptin and food intake

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Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells

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Editorial Material Endocrinology & Metabolism

Role of Endothelial Dysfunction and Arterial Stiffness in the Development of Diabetic Retinopathy

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DIABETES CARE (2015)

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Review Biotechnology & Applied Microbiology

Nitric Oxide, Oxidative Stress, and p66Shc Interplay in Diabetic Endothelial Dysfunction

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BIOMED RESEARCH INTERNATIONAL (2014)

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Review Cell Biology

Iron and Diabetes Risk

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CELL METABOLISM (2013)

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Article Endocrinology & Metabolism

The vascular endothelium in diabetes-a therapeutic target?

Kieren J. Mather

REVIEWS IN ENDOCRINE & METABOLIC DISORDERS (2013)

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The Role of Mitochondria in Cellular Iron-Sulfur Protein Biogenesis: Mechanisms, Connected Processes, and Diseases

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COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2013)

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Adipocyte iron regulates adiponectin and insulin sensitivity

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JOURNAL OF CLINICAL INVESTIGATION (2012)

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MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity

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NATURE MEDICINE (2012)

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Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

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AMERICAN JOURNAL OF PATHOLOGY (2011)

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Review Nutrition & Dietetics

Iron Homeostasis and the Inflammatory Response

Marianne Wessling-Resnick

ANNUAL REVIEW OF NUTRITION, VOL 30 (2010)

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Review Endocrinology & Metabolism

Iron Overload in Diabetic Retinopathy: A Cause or a Consequence of Impaired Mechanisms?

Andreea Ciudin et al.

EXPERIMENTAL DIABETES RESEARCH (2010)

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Defective Bone Morphogenic Protein Signaling Underlies Hepcidin Deficiency in HFE Hereditary Hemochromatosis

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HEPATOLOGY (2010)

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CYP1B1 expression promotes the proangiogenic phenotype of endothelium through decreased intracellular oxidative stress and thrombospondin-2 expression

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BLOOD (2009)

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Article Biochemistry & Molecular Biology

Regulation of Mitochondrial Iron Import through Differential Turnover of Mitoferrin 1 and Mitoferrin 2

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MOLECULAR AND CELLULAR BIOLOGY (2009)

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Article Hematology

Overexpression of mitochondrial ferritin causes cytosolic iron depletion and changes cellular iron homeostasis

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BLOOD (2005)

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Review Endocrinology & Metabolism

Mitochondrial diabetes mellitus

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JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION (2002)

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Review Biochemistry & Molecular Biology

The role of heme and iron-sulfur clusters in mitochondrial biogenesis, maintenance, and decay with age

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ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2002)

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