Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease Journal Article
| Authors: | Stockwell, B. R.; Friedmann Angeli, J. P.; Bayir, H.; Bush, A. I.; Conrad, M.; Dixon, S. J.; Fulda, S.; Gascón, S.; Hatzios, S. K.; Kagan, V. E.; Noel, K.; Jiang, X.; Linkermann, A.; Murphy, M. E.; Overholtzer, M.; Oyagi, A.; Pagnussat, G. C.; Park, J.; Ran, Q.; Rosenfeld, C. S.; Salnikow, K.; Tang, D.; Torti, F. M.; Torti, S. V.; Toyokuni, S.; Woerpel, K. A.; Zhang, D. D. |
| Article Title: | 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. 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. © 2017 Elsevier Inc. |
| Keywords: | review; nonhuman; animal; metabolism; animals; cell death; apoptosis; carcinogenesis; dementia; iron; reactive oxygen species; reactive oxygen metabolite; parkinson disease; lipid peroxidation; lipid metabolism; brain hemorrhage; alzheimer disease; oxidation reduction reaction; oxidation-reduction; glutathione; reagent; cerebrovascular accident; neurodegeneration; traumatic brain injury; reperfusion injury; ros; huntington chorea; fatty acid metabolism; amino acid metabolism; transcription factor nrf2; thiol; reduced nicotinamide adenine dinucleotide phosphate; pufa; peroxidation; ferroptosis; iron metabolism; ubidecarenone; cancer; humans; human; priority journal; heat stress; glutathione metabolism |
| Journal Title: | Cell |
| Volume: | 171 |
| Issue: | 2 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2017-10-05 |
| Start Page: | 273 |
| End Page: | 285 |
| Language: | English |
| DOI: | 10.1016/j.cell.2017.09.021 |
| PUBMED: | 28985560 |
| PROVIDER: | scopus |
| PMCID: | PMC5685180 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 2 November 2017 -- Source: Scopus |
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