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. 2018 May 24;16(5):e2006203.
doi: 10.1371/journal.pbio.2006203. eCollection 2018 May.

Unsolved mysteries: How does lipid peroxidation cause ferroptosis? (V体育官网入口)

Huizhong Feng  1 , Brent R Stockwell  1   2
Affiliations

Unsolved mysteries: How does lipid peroxidation cause ferroptosis?

Huizhong Feng et al. PLoS Biol. .

Abstract

Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes-glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases VSports手机版. .

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Pathways regulating ferroptosis.
Summary of ferroptosis mechanisms and signaling pathway. Ferroptosis inducers/sensitizers are colored red. Ferroptosis inhibitors are colored green. 2,2-BP, 2,2-bipyridyl; ACSL4, acyl-CoA synthetase long chain family member 4; ALOX, arachidonate lipoxygenase; BHT, butylated hydroxytoluene; CoQ10, coenzyme Q10; CPX, ciclopirox olamine; DFO, deferoxamine; D-PUFA, deuterated polyunsaturated fatty acids; Fer-1, ferrostatin-1; FIN56, ferroptosis inducer 56; FINO2, ferroptosis inducer endoperoxide; GPX4, glutathione peroxidase 4; GSSG, glutathione disulfide; HMG-CoA, β-hydroxy β-methylglutaryl-CoA; IKE, imidazole ketone erastin; LPCAT3, lysophosphatidylcholine acyltransferase 3; PL-PUFA (PE), polyunsaturated-fatty-acid-containing phospholipids; PL-PUFA(PE)-OOH, polyunsaturated-fatty-acid-containing-phospholipid hydroperoxides; PUFA, polyunsaturated fatty acid; ROS, reactive oxygen species; RSL3, RAS-selective lethal 3
Fig 2
Fig 2. Fenton chemistry and lipid peroxidation in ferroptosis.
There are three steps involved in nonenzymatic lipid peroxidation. The first step is the generation of lipid radicals (initiation). The second step is the creation of new lipid radicals (propagation). The final step is termination, either by antioxidants or another radical. PUFA, polyunsaturated fatty acid.
Fig 3
Fig 3. Subcellular model of the location of lipid peroxidation in ferroptosis.
The red question marks represent the unsolved mysteries discussed in the article. 4-HNE, 4-hydroxynonenal; MDA, malondialdehyde; PL-PUFA(PE)-OOH, polyunsaturated-fatty-acid-containing-phospholipid hydroperoxides; ROS, reactive oxygen species.
See this image and copyright information in PMC

References

    1. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25(3):486–541. Epub 2018/01/25. doi: 10.1038/s41418-017-0012-4 . - DOI - PMC - PubMed
    1. Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017;171(2):273–85. Epub 2017/10/07. doi: "V体育平台登录" 10.1016/j.cell.2017.09.021 ; PubMed Central PMCID: PMCPMC5685180. - DOI - PMC - PubMed
    1. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72. Epub 2012/05/29. doi: 10.1016/j.cell.2012.03.042 ; PubMed Central PMCID: PMCPMC3367386. - DOI - PMC - PubMed
    1. Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M, Shimada K, et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc. 2014;136(12):4551–6. doi: V体育官网入口 - 10.1021/ja411006a . - DOI - PMC - PubMed
    1. Youssef LA, Rebbaa A, Pampou S, Weisberg SP, Stockwell BR, Hod EA, et al. Increased erythrophagocytosis induces ferroptosis in red pulp macrophages in a mouse model of transfusion. Blood. 2018. Epub 2018/04/19. doi: 10.1182/blood-2017-12-822619 . - DOI - PMC - PubMed

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