title: The respiratory-dependent assembly of ANT1 differentially regulates Bax and Ca2+ mediated cytochrome c release.
abstract: The adenine nucleotide translocator (ANT) is a control point of several fundamental cell processes, as diverse as cell energy supply, mitochondrial DNA maintenance, and apoptosis. This paper describes six individual structures of the carrier, distinguished according to ANT1 oligomeric and conformational states, as well as associations with other proteins. Transitions between these structures depend on energy demand and thus contribute to a metabolic reserve of oxidative phosphorylation (OXPHOS) activity. Moreover, at low respiratory chain activity, we demonstrate that, unlike a mitochondrial Ca2+ upload, Bax, a pro-apoptotic Bcl-2-family protein, is able to trigger a massive release of cytochrome c from one of these ANT1 structures. These new insights emphasize the close relationship between structural rearrangements of ANT and molecular apoptotic events at distinct cell energy levels. OXPHOS functioning has to therefore be considered a crucial control point for the events leading to these contrasting pathways.
authors.affiliation: INSERM U688, Universite Victor Segalen-Bordeaux 2, Bordeaux, France.
authors.forename: Faustin
authors.initials: F
authors.lastname: Benjamin
authors.forename: Rossignol
authors.initials: R
authors.lastname: Rodrigue
authors.forename: Deniaud
authors.initials: D
authors.lastname: Aurelien
authors.forename: Rocher
authors.initials: R
authors.lastname: Christophe
authors.forename: Claverol
authors.initials: C
authors.lastname: Stephane
authors.forename: Malgat
authors.initials: M
authors.lastname: Monique
authors.forename: Brenner
authors.initials: B
authors.lastname: Catherine
authors.forename: Letellier
authors.initials: L
authors.lastname: Thierry
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D011487:Protein Conformation; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D033741:Adenine Nucleotide Translocator 1; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D002118:Calcium