Phospholipase iPLA₂β averts ferroptosis by eliminating a redox lipid death signal.

ABSTRACT: Ferroptosis, triggered by discoordination of iron, thiols and lipids, leads to the accumulation of 15-hydroperoxy (Hp)-arachidonoyl-phosphatidylethanolamine (15-HpETE-PE), generated by complexes of 15-lipoxygenase (15-LOX) and a scaffold protein, phosphatidylethanolamine (PE)-binding protein (PEBP)1. As the Ca²⁺-independent phospholipase A₂β (iPLA₂β, PLA2G6 or PNPLA9 gene) can preferentially hydrolyze peroxidized phospholipids, it may eliminate the ferroptotic 15-HpETE-PE death signal. Here, we demonstrate that by hydrolyzing 15-HpETE-PE, iPLA₂β averts ferroptosis, whereas its genetic or pharmacological inactivation sensitizes cells to ferroptosis. Given that PLA2G6 mutations relate to neurodegeneration, we examined fibroblasts from a patient wit

SUBMITTER: Sun WY 

PROVIDER: S-EPMC8152680 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature