Vahsen, N. et al. AIF deficiency compromises oxidative phosphorylation. EMBO J. 23, 4679-4689

CNRS-UMR8125, Institut Gustave Roussy, Villejuif, France.
The EMBO Journal (Impact Factor: 10.75). 12/2004; 23(23):4679-89. DOI: 10.1038/sj.emboj.7600461
Source: PubMed

ABSTRACT Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that, after apoptosis induction, translocates to the nucleus where it participates in apoptotic chromatinolysis. Here, we show that human or mouse cells lacking AIF as a result of homologous recombination or small interfering RNA exhibit high lactate production and enhanced dependency on glycolytic ATP generation, due to severe reduction of respiratory chain complex I activity. Although AIF itself is not a part of complex I, AIF-deficient cells exhibit a reduced content of complex I and of its components, pointing to a role of AIF in the biogenesis and/or maintenance of this polyprotein complex. Harlequin mice with reduced AIF expression due to a retroviral insertion into the AIF gene also manifest a reduced oxidative phosphorylation (OXPHOS) in the retina and in the brain, correlating with reduced expression of complex I subunits, retinal degeneration, and neuronal defects. Altogether, these data point to a role of AIF in OXPHOS and emphasize the dual role of AIF in life and death.

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    • "One such pathway may be the translocation of Aif1p, the yeast apoptosis inducing factor, from the mitochondria to the nucleus in response to acetic acid (Wissing et al., 2004). Mammalian AIF is a bifunctional NADH oxidase which has a pro-survival role when localized in the mitochondrial intermembrane space through its involvement in mitochondrial respiration, and a lethal function upon translocation to the nucleus through a caspase-independent apoptotic process (Vahsen et al., 2004 ; Susin et al., 1999). Yeast Aif1p shares the same localization and death executing pathways as mammalian AIF, and dependence on cyclophilin A (CypA) but is partially dependent on caspase action (Wissing et al., 2004). "
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