TY - JOUR
AU - Stockwell, Brent R.
AB - Ferroptosis is a non-apoptotic form of regulated cell death caused by the failure of the glutathione-dependent lipid-peroxide-scavenging network. FINO2 is an endoperoxide-containing 1,2-dioxolane that can initiate ferroptosis selectively in engineered cancer cells. We investigated the mechanism and structural features necessary for ferroptosis initiation by FINO2. We found that FINO2 requires both an endoperoxide moiety and a nearby hydroxyl head group to initiate ferroptosis. In contrast to previously described ferroptosis inducers, FINO2 does not inhibit system xc− or directly target GPX4, as do erastin and RSL3, respectively, or deplete GPX4 protein, as does FIN56. Instead, FINO2 causes both indirect loss of GPX4 enzymatic function and directly oxidizes iron, ultimately causing widespread lipid peroxidation. These findings suggest that endoperoxides such as FINO2 can initiate a multi-pronged mechanism of ferroptosis.
TI - FINO2 Initiates Ferroptosis Through GPX4 Inactivation and Iron Oxidation
JF - Nature chemical biology
DO - 10.1038/s41589-018-0031-6
DA - 2018-04-02
UR - https://www.deepdyve.com/lp/pubmed-central/fino2-initiates-ferroptosis-through-gpx4-inactivation-and-iron-EXnjq00y0T
SP - 507
EP - 515
VL - 14
IS - 5
DP - DeepDyve
ER -