Functions both as NADH oxidoreductase and as regulator of apoptosis (PubMed:
20362274, PubMed:
23217327, PubMed:
17094969). In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway. The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA (By similarity). Binds to DNA in a sequence-independent manner (PubMed:
27178839). Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis (PubMed:
17094969). Plays a critical role in caspase- independent, pyknotic cell death in hydrogen peroxide-exposed cells (PubMed:
19418225). In contrast, participates in normal mitochondrial metabolism. Plays an important role in the regulation of respiratory chain biogenesis by interacting with CHCHD4 and controlling CHCHD4 mitochondrial import (PubMed:
26004228).