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The pathological role of ferroptosis in ischemia/reperfusion-related injury

Hong-Fa Yan Qing-Zhang Tuo Qiao-Zhi Yin Peng Lei

Hong-Fa Yan, Qing-Zhang Tuo, Qiao-Zhi Yin, Peng Lei. The pathological role of ferroptosis in ischemia/reperfusion-related injury. Zoological Research, 2020, 41(3): 220-230. doi: 10.24272/j.issn.2095-8137.2020.042
Citation: Hong-Fa Yan, Qing-Zhang Tuo, Qiao-Zhi Yin, Peng Lei. The pathological role of ferroptosis in ischemia/reperfusion-related injury. Zoological Research, 2020, 41(3): 220-230. doi: 10.24272/j.issn.2095-8137.2020.042


doi: 10.24272/j.issn.2095-8137.2020.042

The pathological role of ferroptosis in ischemia/reperfusion-related injury

Funds: This study was supported by grants from the Ministry of Science and Technology of China (2018YFC1312300), National Natural Science Foundation of China (81722016, 81801182), Sichuan Science and Technology Program (2018JPT0037, 2018SZ0190), and China Postdoctoral Science Foundation (2017M623041)
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  • 摘要:


  • Figure  1.  Changes in the cytoplasmic environment during ischemia

    After ischemia, the amount of ATP in cells decreased with the lack of tissue energy supply. The resting potential maintained by active transport breaks down with the large outflow of calcium. Compensatory calcium influx activates downstream calcium-dependent signaling pathways. During this process, the mitochondria produce excess ROS.

    Figure  2.  The indicated pathways control the sensitivity of ferroptosis

    Lipid ROS accumulation is achieved through following major pathways: (1) iron promotes lipid oxidation by Fenton reaction; (2) the arachidonic acid (AA)-containing phosphatidylethanolamine (PE) (AA-PE)/adrenoyl (AdA)-PE is generated by acyl-CoA synthetase long-chain family member 4 (ACSL4) and lysophosphatidylcholine acyltransferase 3 (LPCAT3) and oxidized by lipoxygenases (LOXs). (3) POR can also control lipid peroxidation in ferroptosis by distinct mechanisms. Glutathione (GSH)-dependent glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1)-dependent coenzyme Q10 (CoQ10), as two parallel pathways, control generation of lipid ROS. The accumulation of lipid ROS leads to ferroptosis. PE: Phosphatidylethanolamine; LIP: Labile iron pool; NADPH: Nicotinamide adenine dinucleotide phosphate; Gln: Glutamine; Met: Methionine; Glu: Glutamate; Cys: cysteine; Gly: Glycine; GSSG: Oxidized GSH; GCL: Glutamate-cysteine ligase; GSS: Glutathione synthetase; IREB2: Iron-responsive element binding protein 2; NCOA4: Nuclear receptor coactivator 4; NFS1: Cysteine desulfurase; HO-1: Heme oxygenase-1; POR: Cytochrome P450 oxidoreductase.

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