AIF is a flavoprotein essential for nuclear disassembly in apoptotic cells that is found in the mitochondrial intermembrane space in healthy cells. Induction of apoptosis results in the cleavage of this protein at residue 102 by calpains and/or cathepsins into a soluble and proapoptogenic form that translocates to the nucleus, where it affects chromosome condensation and fragmentation. In addition, this protein induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. AIFM1 also contributes reductase activity in redox metabolism. Mutations in the AIFM1 gene are correlated with Charcot-Marie-Tooth disease (Cowchock syndrome). At a cellular level, AIFM1 mutations result in deficiencies in oxidative phosphorylation, leading to severe mitochondrial encephalomyopathy. Clinical manifestations of this mutation are characterized by muscular atrophy, neuropathy, ataxia, psychomotor regression, hearing loss and seizures.
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