☆ 4.8 Review

Recent advances in small-molecule fluorescent probes for studying ferroptosis

CHEMICAL SOCIETY REVIEWS (2022)

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The molecular mechanisms of ferroptosis and its role in cardiovascular disease

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Summary: Ferroptosis is a programmed iron-dependent cell death characterized by accumulation of lipid peroxides and redox disequilibrium, with unique features compared to other forms of cell death. Metabolic disorders of amino acids, iron, and lipids play a significant role in the pathophysiology of cardiovascular diseases.

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Article Chemistry, Multidisciplinary

A PET-based fluorescent probe for monitoring labile Fe(II) pools in macrophage activations and ferroptosis

Wanjin Xing et al.

Summary: A highly selective and sensitive fluorescent probe (COU-LIP-1) was developed to monitor labile iron(II) pools (LIP) using coumarin 343 as the fluorophore and 3-nitrophenylazanyl ester as both the reactive and fluorescence quenching group. The probe showed a turnon response through a photo-induced photon transfer (PET) mechanism upon Fe(II)-induced reductive cleavage of the N-O bond. It was successfully applied for monitoring labile iron(II) changes in macrophage activations and erastin-induced ferroptosis, providing a powerful tool for selectively sensing LIP under different conditions.

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Kanta Kawai et al.

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Article Chemistry, Analytical

Dual-responsive fluorescent probe for imaging NAD(P)H and mitochondrial viscosity and its application in cancer cell ferroptosis

Han Wei et al.

Summary: The dual-responsive fluorescent probe 3Q-2 can reveal dynamic changes in NAD(P)H and mitochondrial viscosity during ferroptosis, a newly discovered form of cell death. This probe displays two separate spectra in response to NAD(P)H and mitochondrial viscosity with high sensitivity and selectivity. Cancer cells exhibit distinct levels of NAD(P)H and mitochondrial viscosity during ferroptosis induced by specific inhibitors. This robust method of detecting NAD(P)H and mitochondrial viscosity simultaneously may find applications in various physiological and pathological scenarios.

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Near-infrared fluorescent probe for hydrogen sulfide: high-fidelity ferroptosis evaluation in vivo during stroke

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Ya-Lin Qi et al.

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

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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.

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Monitoring the different changing behaviors of •OH and cysteine in two ferroptosis pathways by a dual-functional fluorescence probe

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Summary: Ferroptosis is an iron-dependent mode of regulated cell death, which has attracted significant research interest due to its potential pathological roles and therapeutic functions. In this study, a dual-functional fluorescence probe Coum-HCy was developed for selective and sequential detection of hydroxyl radical (·OH) and cysteine (Cys). The results showed that ·OH was significantly generated during ferroptosis initiated by erastin or RSL3, while the intracellular Cys level decreased when cells were treated with erastin but remained unaffected by RSL3. This probe may provide valuable insights into the mutual correlation between ·OH and Cys during ferroptosis.

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Article Chemistry, Multidisciplinary

Unique assembly of carbonylpyridinium and chromene reveals mitochondrial thiol starvation under ferroptosis and novel ferroptosis inducer

Kaiqing Ma et al.

Summary: Researchers developed a new probe CM-Mit for accurate detection of thiols in mitochondria. The probe has fast response and protein labeling ability, preventing diffusion out of the mitochondria, and can be used for drug screening and studying ferroptosis.

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3D two-photon brain imaging reveals dihydroartemisinin exerts antiepileptic effects by modulating iron homeostasis

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Ferroptosis: machinery and regulation

Xin Chen et al.

Summary: Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation. Lipoxygenase is the main promoter of ferroptosis, while GPX4 is the central repressor of this process.

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Dan Cheng et al.

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Ferroptosis: molecular mechanisms and health implications

Daolin Tang et al.

Summary: Cell death can be executed through different subroutines, such as ferroptosis which is an iron-dependent form of non-apoptotic cell death. Ferroptosis can occur through two major pathways, driven by redox imbalance and abnormal expression of redox-active enzymes. The process is precisely regulated at multiple levels, with the transcription factor NFE2L2 playing a central role in anti-ferroptotic defense.

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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.

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Revealing the Viscosity Changes in Lipid Droplets during Ferroptosis by the Real-Time and In Situ Near-Infrared Imaging

Baoli Dong et al.

Summary: The study revealed the changes of lipid droplets viscosity during ferroptosis using a novel viscosity-sensitive near-infrared fluorescent probe. The experiment results showed a significant increase in lipid droplets viscosity during ferroptosis, while there was nearly no change in cells treated with ferroptosis inhibitors simultaneously.

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Broadening horizons: the role of ferroptosis in cancer

Xin Chen et al.

Summary: Ferroptosis is an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, and can be induced by various agents to suppress tumor growth while also potentially triggering inflammation-associated immunosuppression. The extent of ferroptosis's impact on tumor biology and its interactions with other signaling pathways are still under investigation.

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Designing an ESIPT-based fluorescent probe for imaging of hydrogen peroxide during the ferroptosis process

Han-Chen Zhang et al.

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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY (2021)

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A biotin-guided two-photon fluorescent probe for detection of hydrogen peroxide in cancer cells ferroptosis process

Mingguang Ren et al.

Summary: A biotin-guided, two-photon fluorescent probe was developed for sensitive detection of H2O2 in cancer cells, showing potential as a tumor-targeting H2O2 biosensor.

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NUPR1 is a critical repressor of ferroptosis

Jiao Liu et al.

Summary: Ferroptosis is a type of iron-dependent regulated cell death, and the stress-inducible transcription factor NUPR1 may drive resistance to ferroptosis by mediating LCN2 expression. Blocking the NUPR1-LCN2 pathway can increase ferroptosis inducer activity and worsen conditions like pancreatitis in relevant mouse models.

NATURE COMMUNICATIONS (2021)

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Review Cell Biology

Ferroptosis and Its Modulation by Autophagy in Light of the Pathogenesis of Lysosomal Storage Diseases

Karolina Pierzynowska et al.

Summary: Ferroptosis is a type of cell death dependent on factors like iron accumulation and lipid peroxidation. Recent discovery of autophagy-dependent ferroptosis pathways has brought attention to its role in lysosomal storage diseases. modulation of ferroptosis markers and possible involvement of autophagy-dependent ferroptosis are highlighted in LSD.

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A Polarity-Sensitive Ratiometric Fluorescence Probe for Monitoring Changes in Lipid Droplets and Nucleus during Ferroptosis

Kang-Nan Wang et al.

Summary: This study introduces the first LD/nucleus dual-targeted ratiometric fluorescent probe, CQPP, to monitor polarity changes in the cellular microenvironment. Through the application of CQPP, it was found that LD polarity increased in the ferroptosis model, while the polarity between LDs and cytoplasm homogenized.

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DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer

Chao Mao et al.

Summary: The study reveals the mechanism of ferroptosis induced by inhibiting GPX4 in cancer cells, as well as the potential pathways to enhance or inhibit ferroptosis by intervening in relevant metabolic pathways. Therapeutic strategies targeting different levels of GPX4 expression could be a promising new approach for cancer treatment.

NATURE (2021)

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Ferroptosis and its emerging roles in cardiovascular diseases

Ning Li et al.

Summary: Ferroptosis, a novel form of regulated cell death driven by iron-dependent lipid peroxidation, has been found to play a role in various cardiovascular diseases, but the specific mechanisms by which it contributes to the progression of cardiovascular diseases remain unclear.

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Yue Zheng et al.

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Monitoring hydrogen polysulfide during ferroptosis with a two-photon fluorescent probe

Xiaojiao Di et al.

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Potentiation of glutathione loss and nerve cell death by the transition metals iron and copper: Implications for age-related neurodegenerative diseases

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Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma

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Aggregation-Induced Emission Luminogens: Union Is Strength, Gathering Illuminates Healthcare

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BID links ferroptosis to mitochondrial cell death pathways

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Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems

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MOLECULAR BIOSYSTEMS (2015)

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Hydrogen sulfide and polysulfides as signaling molecules

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Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death

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Review Biochemistry & Molecular Biology

Hydrogen Sulfide: A Neuromodulator and Neuroprotectant in the Central Nervous System

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Redox chemistry and chemical biology of H2S, hydropersulfides, and derived species: Implications of their possible biological activity and utility

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Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice

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Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling

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AUTOPHAGY (2013)

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Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

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Physiological role of hydrogen sulfide and polysulfide in the central nervous system

Hideo Kimura

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Hydrogen Sulfide in Biochemistry and Medicine

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Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

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Highly reactive oxygen species: detection, formation, and possible functions

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Reaction of Hydrogen Sulfide with the Neutrophil Oxidant Hypochlorous Acid to Generate Polysulfides

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CHEMICAL RESEARCH IN TOXICOLOGY (2010)

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Reactive oxygen species, cellular redox systems, and apoptosis

Magdalena L. Circu et al.

FREE RADICAL BIOLOGY AND MEDICINE (2010)

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Quantitative reactivity profiling predicts functional cysteines in proteomes

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Article Cell Biology

Hypoxia induces autophagic cell death in apoptosis-competent cells through a mechanism involving BNIP3

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AUTOPHAGY (2008)

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Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells

Wan Seok Yang et al.

CHEMISTRY & BIOLOGY (2008)

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Hydrogen sulphide and its therapeutic potential

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RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels

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Hydrogen peroxide sensing and signaling

Elizabeth A. Veal et al.

MOLECULAR CELL (2007)

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Autophagy in metazoans: Cell survival in the land of plenty

JJ Lum et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2005)

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Antimicrobial reactive oxygen and nitrogen species: Concepts and controversies

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Activation of ATP-sensitive K+ (KATP) channels by H2O2 underlies glutamate-dependent inhibition of striatal dopamine release

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

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Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells

S Dolma et al.

CANCER CELL (2003)

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The labile iron pool: Characterization, measurement, and participation in cellular processes

O Kakhlon et al.

FREE RADICAL BIOLOGY AND MEDICINE (2002)

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Article Biochemistry & Molecular Biology

Relationship between the occurrence of cysteine in proteins and the complexity of organisms

A Miseta et al.

MOLECULAR BIOLOGY AND EVOLUTION (2000)

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Article Cell Biology

Antimicrobial and cytotoxic activity of hypochlorous acid: interactions with taurine and nitrite

J Marcinkiewicz et al.

INFLAMMATION RESEARCH (2000)

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