Fig. 3

Snapshot of ferroptosis execution and its major defense mechanisms. Ferroptosis is executed by excessive peroxidation of PUFA-containing PLs within cellular membranes. This free radical chain reaction is catalyzed by O₂ and Fe²⁺. Two major defense mechanisms suppress the process of PL peroxidation: (1) direct conversion of reactive PL-OOH to unreactive PL-OH by GPX4, and (2) dampening by an arsenal of lipophilic radical traps, such as vitamin E, A or KH₂, BH4, 7-DHC, and CoQ10H₂. BH4, tetrahydrobiopterin; CoQ10H₂, reduced form of coenzyme Q10; DHODH, dihydroorotate dehydrogenase; FSP1, ferroptosis suppressor protein 1; GCH1, GTP cyclohydrolase 1; GPX4, glutathione peroxidase 4; GSH, glutathione (reduced form); GSSG, glutathione disulfide (oxidized form)