Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
- PMID: 28985560
- PMCID: PMC5685180
- DOI: 10.1016/j.cell.2017.09.021
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Abstract
Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.
Keywords: PUFA; ROS; cancer; cell death; ferroptosis; glutathione; iron; metabolism; neurodegeneration; peroxidation.
Copyright © 2017 Elsevier Inc. All rights reserved.
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Reply to "Ferroptosis in the colon epithelial cells as a therapeutic target for ulcerative colitis".J Gastroenterol. 2024 Jan;59(1):77-78. doi: 10.1007/s00535-023-02064-w. Epub 2023 Nov 27. J Gastroenterol. 2024. PMID: 38008824 No abstract available.
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References
-
- Angeli JPF, Shah R, Pratt DA, Conrad M. Ferroptosis Inhibition: Mechanisms and Opportunities. Trends Pharmacol Sci. 2017;38:489–498. - PubMed
-
- Ayton S, Fazlollahi A, Bourgeat P, Raniga P, Ng A, Lim YY, Diouf I, Farquharson S, Fripp J, Ames D, et al. Cerebral quantitative susceptibility mapping predicts β-amyloid-related cognitive decline. Brain. 2017 in press. - PubMed
-
- Bannai S, Tsukeda H, Okumura H. Effect of antioxidants on cultured human diploid fibroblasts exposed to cystine-free medium. Biochem Biophys Res Commun. 1977;74:1582–1588. - PubMed
-
- Barelli H, Antonny B. Lipid unsaturation and organelle dynamics. Curr Opin Cell Biol. 2016;41:25–32. - PubMed
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