FINO₂ initiates ferroptosis through GPX4 inactivation and iron oxidation.

ABSTRACT: 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 x_c^- or directly target the reducing enzyme GPX4, as do erastin and RSL3, respectively, nor does it deplete GPX4 protein, as does FIN56. Instead, FINO₂ bo

SUBMITTER: Gaschler MM 

PROVIDER: S-EPMC5899674 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature