Apoptosis-inducing factor (AIFM1, AIF, PDCD8) is a ubiquitously expressed flavoprotein that plays a critical role in caspase-independent apoptosis. AIF 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 AIF leads to early apoptotic events, such as chromatin condensation and large-scale DNA fragmentation. Studies of AIF knockout mice have shown that the apoptotic activity of AIF is cell type and stimuli-dependent. Also noted was that AIF was required for embryoid body cavitation, representing the first wave of programmed cell death during embryonic morphogenesis. Structural analysis of AIF revealed two regions, an oxidoreductase activity and a DNA binding domain. AIF 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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