Apoptosis-inducing factor (AIFM1, AIF, PDCD8) is a ubiquitously expressed flavoprotein that plays a critical role in caspase-independent apoptosis. AIFM1 is expressed as a 66 kDa precursor protein before being N-terminally cleaved to 62 kDa and localized to the mitochondrial intermembrane space. In response to apoptotic stimuli, AIFM1 is released from the mitochondrial intermembrane as a 57 kDa fragment that can translocate to the nucleus. Treatment of isolated nuclei with recombinant AIFM1 leads to early apoptotic events, such as chromatin condensation and large-scale DNA fragmentation. Studies of AIFM1 knockout mice have shown that the apoptotic activity of AIFM1 is cell type and stimuli-dependent. AIFM1 has been implicated in oxeiptosis, a non-inflammatory, caspase independent cell death pathway caused by oxidative stress. During oxeiptosis, increased reactive oxygen species cause the release of the phosphatase PGAM5 from KEAP1 leading to dephosphorylation of AIFM1 (Ser-116) and subsequent cell death. Thus, AIFM1 phosphorylation status at Ser-116 may be an important marker for cell death involving oxeiptosis.
Lipton, S.A. and Bossy-Wetzel, E. (2002) Cell 111:147.
Daugas, E. et al. (2000) FEBS Lett. 476:118.
*For more information, see UniProt Accession O95831
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*All molecular weights (MW) are confirmed by comparison to Bio-Rad Rainbow Markers and to western blot mobilities of known proteins with similar MW.
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