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. Also, AIFM1 was required for embryoid body cavitation, representing the first wave of programmed cell death during embryonic morphogenesis. Structural analysis of AIFM1 revealed two regions, an oxidoreductase activity and a DNA binding domain. AIFM1 has dual functions, a pro-apoptotic activity in the nucleus via its DNA binding and an anti-apoptotic activity via the scavenging of free radicals through its oxidoreductase activity.

References

*For more information, see UniProt Accession O95831

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