AIFM2 Protein, Human (Strep)

AIFM2 is a NAD(P)H-dependent oxidoreductase that serves as a key inhibitor of ferroptosis. At the plasma membrane, it catalyzes the reduction of coenzyme Q/ubiquinone-10 to ubiquinol-10, a lipophilic radical-trapping antioxidant that prevents lipid oxidative damage and subsequent ferroptosis. It acts in parallel with GPX4 to suppress phospholipid peroxidation and ferroptosis, with this anti-ferroptotic function being independent of cellular glutathione levels. Additionally, AIFM2 functions as a potent radical-trapping antioxidant by mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle: it catalyzes NAD(P)H-dependent reduction of vitamin K (phylloquinone, menaquinone-4, and menadione) to hydroquinone forms, which act as potent inhibitors of phospholipid peroxidation and ferroptosis. AIFM2 may participate in mitochondrial stress signaling: under oxidative stress, it associates with the lipid peroxidation end product 4-hydroxy-2-nonenal (HNE) to form a lipid adduct lacking oxidoreductase activity, which then translocates from mitochondria to the nucleus, triggering DNA damage and cell death. It is also capable of non-sequence-specific DNA binding.