Fig. 6.

Graphic illustration of the function of FAF1 in protecting cells from ferroptosis. In the presence of FAF1, free AA is sequestered into a lipid–protein complex that prevents their access to Fe²⁺. In the absence of FAF1, free AA is more easily accessible to Fe²⁺, resulting in increased peroxidation of the fatty acids. The PUFA peroxides produced may be converted to PUFA radicals, which can enter phospholipid bilayers to catalyze peroxidation of PUFA-containing phospholipids, the formation of which depends on ACSL4-catalyzed activation of PUFAs. Ferroptosis may be triggered when the amount of peroxidized phospholipids produced overwhelms the scavenging activity of GPX4.