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

Research output: Contribution to journalArticlepeer-review

Abstract

Apoptosis-inducing factor (AIF) is a mitochondrial flavo-protein 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.

Original languageEnglish
Pages (from-to)4679-4689
Number of pages11
JournalEMBO Journal
Volume23
Issue number23
DOIs
Publication statusPublished - Nov 24 2004

Keywords

  • Apoptosis
  • Mitochondria
  • Oxidative phosphorylation
  • Programmed cell death

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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