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Article

  • The EMBO Journal (2004) 23, 4679 - 4689
  • doi:10.1038/sj.emboj.7600461

Published online: 4 November 2004

AIF deficiency compromises oxidative phosphorylation

Nicola Vahsen1, Céline Candé1, Jean-Jacques Brière2, Paule Bénit2, Nicholas Joza3, Nathanael Larochette1, Pier Giorgio Mastroberardino4, Marie O Pequignot1, Noelia Casares1, Vladimir Lazar5, Olivier Feraud6, Najet Debili6, Silke Wissing7, Silvia Engelhardt7, Frank Madeo7, Mauro Piacentini4, Josef M Penninger3, Hermann Schägger8,9, Pierre Rustin2,9 and Guido Kroemer1,9

  1. CNRS-UMR8125, Institut Gustave Roussy, Villejuif, France
  2. INSERM U393, Service de Génétique, Hôpital Necker-Enfants Malades, France
  3. IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
  4. Department of Biology, University of Rome Tor Vergata, Rome, Italy
  5. Unité de Génomique Fonctionelle, Institut Gustave Roussy, Villejuif, France
  6. INSERM U362, Institut Gustave Roussy, Villejuif, France
  7. Physiologisch-chemisches Institut, Tübingen, Germany
  8. Institut für Biochemie I, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany
  9. These authors share senior co-authorship

Correspondence to:

Guido Kroemer, CNRS-UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39, rue Camille Desmoulins, 94805 Villejuif, France. Tel.: +33 1 42 11 60 46; Fax: +33 1 42 11 52 44; E-mail: kroemer@igr.fr

Received 18 June 2004; Accepted 5 October 2004

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.

  • Keywords:

    • apoptosis,
    • mitochondria,
    • oxidative phosphorylation,
    • programmed cell death