Ferroptosis: mechanisms, biology and role in disease

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(4), P. 266 - 282

Published: Jan. 25, 2021

Language: Английский

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Ferroptosis: molecular mechanisms and health implications

Cell Research, Journal Year: 2020, Volume and Issue: 31(2), P. 107 - 125

Published: Dec. 2, 2020

Abstract Cell death can be executed through different subroutines. Since the description of ferroptosis as an iron-dependent form non-apoptotic cell in 2012, there has been mounting interest process and function ferroptosis. Ferroptosis occur two major pathways, extrinsic or transporter-dependent pathway intrinsic enzyme-regulated pathway. is caused by a redox imbalance between production oxidants antioxidants, which driven abnormal expression activity multiple redox-active enzymes that produce detoxify free radicals lipid oxidation products. Accordingly, precisely regulated at levels, including epigenetic, transcriptional, posttranscriptional posttranslational layers. The transcription factor NFE2L2 plays central role upregulating anti-ferroptotic defense, whereas selective autophagy may promote ferroptotic death. Here, we review current knowledge on integrated molecular machinery describe how dysregulated involved cancer, neurodegeneration, tissue injury, inflammation, infection.

Language: Английский

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Broadening horizons: the role of ferroptosis in cancer

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(5), P. 280 - 296

Published: Jan. 29, 2021

Language: Английский

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The molecular machinery of regulated cell death

Cell Research, Journal Year: 2019, Volume and Issue: 29(5), P. 347 - 364

Published: April 4, 2019

Cells may die from accidental cell death (ACD) or regulated (RCD). ACD is a biologically uncontrolled process, whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms. A growing number of novel non-apoptotic forms have been identified are increasingly being implicated in various human pathologies. Here, we critically review the current state art regarding types RCD, including necroptosis, pyroptosis, ferroptosis, entotic death, netotic parthanatos, lysosome-dependent autophagy-dependent alkaliptosis oxeiptosis. The in-depth comprehension each these lethal subroutines their intercellular consequences uncover therapeutic targets for avoidance pathogenic loss.

Language: Английский

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Targeting Ferroptosis to Iron Out Cancer

Cancer Cell, Journal Year: 2019, Volume and Issue: 35(6), P. 830 - 849

Published: May 16, 2019

Language: Английский

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

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2401 - 2421

Published: July 1, 2022

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, was identified as distinct phenomenon and named decade ago. Ferroptosis has been implicated in broad set biological contexts, from development to aging, immunity, cancer. This review describes key regulators this within framework metabolism, ROS biology, iron biology. Key concepts major unanswered questions the ferroptosis field are highlighted. The next promises yield further breakthroughs mechanisms governing additional ways harnessing for therapeutic benefit.

Language: Английский

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Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy

Protein & Cell, Journal Year: 2020, Volume and Issue: 12(8), P. 599 - 620

Published: Oct. 1, 2020

Abstract The cystine/glutamate antiporter SLC7A11 (also commonly known as xCT) functions to import cystine for glutathione biosynthesis and antioxidant defense is overexpressed in multiple human cancers. Recent studies revealed that overexpression promotes tumor growth partly through suppressing ferroptosis, a form of regulated cell death induced by excessive lipid peroxidation. However, cancer cells with high expression (SLC7A11 ) also have endure the significant cost associated SLC7A11-mediated metabolic reprogramming, leading glucose- glutamine-dependency cells, which presents potential vulnerabilities therapeutic targeting cancer. In this review, we summarize diverse regulatory mechanisms cancer, discuss ferroptosis-dependent -independent promoting development, explore mechanistic basis SLC7A11-induced nutrient dependency conceptualize strategies target treatment. This review will provide foundation further understanding dependency, biology developing novel effective therapies.

Language: Английский

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Targeting ferroptosis as a vulnerability in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(7), P. 381 - 396

Published: March 25, 2022

Language: Английский

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Ferroptosis: machinery and regulation

Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2054 - 2081

Published: Aug. 19, 2020

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which controlled integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase the main promoter ferroptosis producing hydroperoxides, its function relies on activation ACSL4-dependent biosynthesis. In contrast, selenium-containing GPX4 currently recognized as a central repressor ferroptosis, activity depends glutathione produced from cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, amino acids) degradation pathways (macroautophagy/autophagy ubiquitin-proteasome system) orchestrate complex ferroptotic response through direct or indirect regulation iron accumulation peroxidation. Although detailed mechanism membrane injury during remains mystery, ESCRT III-mediated plasma repair can make cells resistant to ferroptosis. Here, we review recent rapid progress in understanding molecular mechanisms focus epigenetic, transcriptional, posttranslational this process.Abbreviations: 2ME: beta-mercaptoethanol; α-KG: α-ketoglutarate; ccRCC: clear renal carcinoma; EMT: epithelial-mesenchymal transition; FAO: fatty acid beta-oxidation; GSH: glutathione; MEFs: mouse embryonic fibroblasts; MUFAs: monounsaturated acids; NO: nitric oxide; NOX: NADPH oxidase; PPP: pentose phosphate pathway; PUFA: polyunsaturated acid; RCD: death; RNS: reactive nitrogen species; ROS: oxygen RTAs: radical-trapping antioxidants; UPS: system; UTR: untranslated region.

Language: Английский

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Recent Progress in Ferroptosis Inducers for Cancer Therapy

Advanced Materials, Journal Year: 2019, Volume and Issue: 31(51)

Published: Oct. 8, 2019

Abstract Ferroptosis is a newly discovered form of regulated cell death that the nexus between metabolism, redox biology, and human health. Emerging evidence shows potential triggering ferroptosis for cancer therapy, particularly eradicating aggressive malignancies are resistant to traditional therapies. Recently, there has been great deal effort design develop anticancer drugs based on induction. Recent advances ferroptosis‐inducing agents at intersection chemistry, materials science, biology presented. The basis summarized first highlight feasibility characteristics therapy. A literature review inducers (including small molecules nanomaterials) then presented delineate their design, action mechanisms, applications. Finally, some considerations research spotlighted, followed by discussion challenges future development directions this burgeoning field.

Language: Английский

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