Peroxisome: the new player in ferroptosis

A recent paper published in Nature by Zou et al. reported that peroxisomes, membrane-bound oxidative organelles, contribute to ferroptosis through the biosynthesis of plasmalogens for lipid peroxidation (Fig. 1 ). 1 These observations provide new insights into the lipid metabolic basis of ferroptotic cell death. Fig. 1 Peroxisome-dependent and independent initiation of ferroptotic pathways. The peroxidation of PUFAs by ALOXs or POR to produce LOOH is an important step in promoting ferroptosis. The synthesis of PUFA-plasmalogen and AA/AdA-PE is mediated by peroxisome-dependent and independent pathways, respectively. Ferroptosis is suppressed by the lipid peroxidation repair enzyme GPX4 and the ESCRT-III membrane repair machinery. AA/AdA arachidonic acid/adrenic acid, AA/AdA-CoA, arachidonic acid/adrenic acid-coenzyme A, AA/AdA-CoA-PE arachidonic acid/adrenic acid-coenzyme A-phosphatidylethanolamine, Ac-CoA acetyl coenzyme A, ACSL4 acyl-CoA synthetase long-chain family member 4, ALOX lipoxygenase, AGPS alkylglycerone phosphate synthase, AGP 1-O-alkyl-glycerol-3-phosphate, AGPAT3 1-acylglycerol-3-phosphate O-acyltransferase 3, DHAP dihydroxyacetone phosphate, ESCRT-III endosomal sorting complexes required for transport-III, FAR1 fatty acyl-CoA reductase 1, GPX4 glutathione peroxidase 4, GNPAT glyceronephosphate O-acyltransferase, LPCAT3 lysophosphatidylcholine acyltransferase 3, LOOH lipid hydroperoxides, POR cytochrome P450 oxidoreductase, PUFAs polyunsaturated fatty acids, PEDS1/TMEM189 plasmanylethanolamine desaturase 1 Full size image