A Cell Cycle-Dependent Ferroptosis Sensitivity Switch Governed by EMP2.

ABSTRACT: Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation. Ferroptosis can be induced by system x_c^- cystine/glutamate antiporter inhibition or by direct inhibition of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). The regulation of ferroptosis in response to system x_c^- inhibition versus direct GPX4 inhibition may be distinct. Here, we show that cell cycle arrest enhances sensitivity to ferroptosis triggered by GPX4 inhibition but not system x_c^- inhibition. Arrested cells have increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids, which drives sensitivity to GPX4 inhibition. Epithelial membrane protein 2 (EMP2) expression is reduced upo

SUBMITTER: Rodencal J 

PROVIDER: S-EPMC10370086 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature