title: AIF deficiency compromises oxidative phosphorylation.
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.
authors.affiliation: CNRS-UMR8125, Institut Gustave Roussy, Villejuif, France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Vahsen
authors.forename: Céline
authors.initials: C
authors.lastname: Candé
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Brière
authors.forename: Paule
authors.initials: P
authors.lastname: Bénit
authors.forename: Nicholas
authors.initials: N
authors.lastname: Joza
authors.forename: Nathanael
authors.initials: N
authors.lastname: Larochette
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Mastroberardino
authors.forename: Marie O
authors.initials: MO
authors.lastname: Pequignot
authors.forename: Noelia
authors.initials: N
authors.lastname: Casares
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.forename: Olivier
authors.initials: O
authors.lastname: Feraud
authors.forename: Najet
authors.initials: N
authors.lastname: Debili
authors.forename: Silke
authors.initials: S
authors.lastname: Wissing
authors.forename: Silvia
authors.initials: S
authors.lastname: Engelhardt
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Hermann
authors.initials: H
authors.lastname: Schägger
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D042967:Electron Transport Complex I / Q000096:biosynthesis; D014450:Electron Transport Complex III / Q000096:biosynthesis; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D010085:Oxidative Phosphorylation; D010802:Phylogeny; D034741:RNA, Small Interfering / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D015003:Yeasts / Q000235:genetics / Q000254:growth & development / Q000378:metabolism
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; C494830:AIFM1 protein, mouse; D034741:RNA, Small Interfering; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D005947:Glucose