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AIF deficiency compromises oxidative phosphorylation
Author(s) -
Vahsen Nicola,
Candé Céline,
Brière JeanJacques,
Bénit Paule,
Joza Nicholas,
Larochette Nathanael,
Mastroberardino Pier Giorgio,
Pequignot Marie O,
Casares Noelia,
Lazar Vladimir,
Feraud Olivier,
Debili Najet,
Wissing Silke,
Engelhardt Silvia,
Madeo Frank,
Piacentini Mauro,
Penninger Josef M,
Schägger Hermann,
Rustin Pierre,
Kroemer Guido
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600461
Subject(s) - humanities , art , art history
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.