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PMID: 15526035 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

AIF deficiency compromises oxidative phosphorylation.

The EMBO journal ·Vol. 23 ·No. 23 ·2004-11-24 ·Pages 4679-89

Vahsen N, Candé C, Brière JJ, Bénit P, Joza N, Larochette N, Mastroberardino PG, Pequignot MO, Casares N, Lazar V, Feraud O, Debili N, Wissing S, Engelhardt S, Madeo F, Piacentini M, Penninger JM, Schägger H, Rustin P, Kroemer G

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.

MeSH Terms
Adenosine Triphosphate/biosynthesis Animals Apoptosis Apoptosis Inducing Factor Brain/metabolism Cells, Cultured Electron Transport Complex I/biosynthesis Electron Transport Complex III/biosynthesis Flavoproteins/genetics,metabolism Glucose/metabolism Humans Lactic Acid/biosynthesis Membrane Proteins/deficiency,genetics,metabolism Mice Mice, Transgenic Mitochondria/metabolism Myocardium/metabolism Organ Specificity Oxidative Phosphorylation Phylogeny RNA, Small Interfering/metabolism Retina/metabolism Yeasts/genetics,growth & development,metabolism
Chemicals
AIFM1 protein, human Apoptosis Inducing Factor Flavoproteins Membrane Proteins Pdcd8 protein, mouse RNA, Small Interfering Lactic Acid Adenosine Triphosphate Electron Transport Complex I Electron Transport Complex III Glucose
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Vahsen Nicola
CNRS-UMR8125, Institut Gustave Roussy, Villejuif, France.
Candé Céline
Brière Jean-Jacques
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
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600461
Published
2004-11-24
Epub
2004-00-04
Pages
4679-89
Language
English
Region
England
NLM ID
8208664
PMCID
PMC533047
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600461 PMC Full Text View journal details
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