SLC25A22 as a Key Mitochondrial Transporter Against Ferroptosis by Producing Glutathione and Monounsaturated Fatty Acids.

ABSTRACT: Aims: Ferroptosis, a type of oxidative cell death driven by unlimited lipid peroxidation, is emerging as a target for cancer therapy. Although mitochondrial dysfunction may lead to ferroptosis, the underlying molecular mechanisms and metabolic pathways for ferroptosis are incompletely understood. Here, we identify solute carrier family 25 member 22 (SLC25A22), a mitochondrial glutamate transporter, as a driver of ferroptosis resistance in pancreatic ductal adenocarcinoma (PDAC) cells. Results: The downregulation of SLC25A22 expression was associated with increased sensitivity to ferroptosis, but not to apoptosis. Mechanistically, on the one hand, SLC25A22-dependent NAPDH synthesis blocks ferroptotic cell death in PDAC cells through mediating the production of gl

SUBMITTER: Liu Y 

PROVIDER: S-EPMC10620438 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature