Ferroptosis suppressor protein 1 (FSP1) (FSP1)

Ferroptosis suppressor protein 1 (FSP1), formerly known as AIFM2, is a critical component of a non-canonical, glutathione-independent antioxidant system that protects cells from ferroptosis (Source: Nature, 2019). It is a myristoylated protein that localizes to the plasma membrane, where it functions as an NADH-dependent oxidoreductase to maintain a pool of reduced Coenzyme Q10 (ubiquinol) (Source: UniProt). This membrane-embedded system acts as a potent radical-trapping antioxidant, effectively neutralizing lipid peroxyl radicals and preventing the lethal accumulation of lipid peroxides (Source: PubMed). FSP1 is frequently upregulated in various cancers, particularly those resistant to GPX4 inhibitors, making it a high-priority therapeutic target for oncology (Source: NIH). Beyond cancer, its role in regulating ferroptosis suggests potential implications in neurodegeneration and organ ischemia-reperfusion injuries (Source: Nature Reviews Cancer).

Other names

AIFM2Apoptosis-inducing factor mitochondria-associated 2AMIDPRG3Apoptosis-inducing factor 2p53-induced gene 3Membrane-embedded antioxidant system

FSP1 functions as a myristoylated, plasma membrane-associated oxidoreductase that reduces Coenzyme Q10 (ubiquinone) to its reduced form, ubiquinol, using NAD(P)H as a cofactor. Ubiquinol then acts as a lipophilic radical-trapping antioxidant (RTA) to neutralize lipid peroxyl radicals, thereby preventing the iron-dependent lipid peroxidation that drives ferroptosis.