Gastroenterology and Hepatology from Bed to Bench

Abstract

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