AMPK-Mediated BECN1 Phosphorylation Promotes Ferroptosis by Directly Blocking System X_c^- Activity.

ABSTRACT: Ferroptosis is a form of regulated cell death triggered by lipid peroxidation after inhibition of the cystine/glutamate antiporter system X_c^-. However, key regulators of system X_c^- activity in ferroptosis remain undefined. Here, we show that BECN1 plays a hitherto unsuspected role in promoting ferroptosis through directly blocking system Xc^- activity via binding to its core component, SLC7A11 (solute carrier family 7 member 11). Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X_c^- inhibitors (e.g., erastin, sulfasalazine, and sorafenib), but not other ferroptosis inducers including RSL3, FIN56, and buthionine sulfoximine. Mechanistically, AMP-activated protein kinase (AMPK)-mediated phosphorylati

SUBMITTER: Song X 

PROVIDER: S-EPMC6081251 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature