Vital functions of Apoptosis Inducing Factor (AIF)

In many models of programmed cell death, the mitochondrial protein AIF translocates to the nucleus, where it induces the chromatin condensation and DNA degradation. However, today it is well established that this flavoprotein is bifunctional. In addition to its lethal function in the nucleus of dying cells, AIF plays a vital bioenergetic role in healthy ones by regulating mainly the activity of the mitochondrial respiratory chain complex I. Hypomorphic or deletion mutants of AIF have led to the generation of the first reliable mouse model of complex I deficiency syndrome, which leads to progressive ataxia and blindness due to neuronal degeneration, as well as a dilated cardiomyopathy, skeletal muscle atrophy and metabolic dysfunction. Here, we discuss recent progress in the quest to understand AIF’s involvement in cell survival and in the regulation of mitochondrial respiratory chain complex I.