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Description

Ferroptosis suppressor protein 1 (UniProt: Q9BRQ8, also known as FSP1, Apoptosis-inducing factor homologous mitochondrion-associated inducer of death, AMID, p53-responsive gene 3 protein, AIFM2) is encoded by the AIFM2 (also known as AMID, PRG3) gene (Gene ID: 84883) in human. AIFM2 is a lipid-anchor membrane protein of the FAD-dependent oxidoreductase family that is also detected in the nucleus and mitochondrial membrane. It is highly expressed in heart and moderately in liver and skeletal muscle. Low expression levels are observed in placenta, lung, kidney, and pancreas. It is reported to be down-regulated in a number of human tumors. It serves as a NAD(P)H-dependent oxidoreductase and is involved in cellular oxidative stress response. At the plasma membrane, it catalyzes reduction of coenzyme Q/ubiquinone-10 to ubiquinol-10, a lipophilic radical-trapping antioxidant that prevents lipid oxidative damage and consequently ferroptosis. It is shown to cooperates with GPX4 to suppress phospholipid peroxidation and ferroptosis and its anti-ferroptotic function is reported to be independent of cellular glutathione levels. It also plays a role in mitochondrial stress signaling. Upon induction of oxidative stress, it associates with the lipid peroxidation end product 4-hydroxy-2-nonenal (HNE) forming a lipid adduct. This HNE adduct inactivates the NADH oxidoreductase activity of AIFM2 and facilitates its translocation from mitochondria into the nucleus triggering DNA damage and cell death. (Ref.: Doll, S., et al. (2019). Nature 575(7784), 693-698, Miriyala, S., et al. (2016). Free Radic. Biol. Med. 91, 68-80).