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AIF deficiency compromises oxidative phosphorylation

  • Nicola Vahsen
  • Céline Candé
  • Jean-Jacques Brière
  • Paule Bénit
  • Nicholas Joza
  • Nathanael Larochette
  • Pier Giorgio Mastroberardino
  • Marie O Pequignot
  • Noelia Casares
  • Vladimir Lazar
  • Olivier Feraud
  • Najet Debili
  • Silke Wissing
  • Silvia Engelhardt
  • Frank Madeo
  • Mauro Piacentini
  • Josef M Penninger
  • Hermann Schägger
  • Pierre Rustin
  • Guido Kroemer
Nature Publishing Group
Publication Date
Nov 04, 2004
  • Biology


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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