title: The mitochondrial ADP/ATP carrier: structural, physiological and pathological aspects.
abstract: Under the conditions of oxidative phosphorylation, the mitochondrial ADP/ATP carrier catalyses the one to one exchange of cytosolic ADP against matrix ATP across the inner mitochondrial membrane. The ADP/ATP transport system can be blocked very specifically by two families of inhibitors: atractyloside (ATR) and carboxyatractyloside (CATR) on one hand, and bongkrekic acid (BA) and isobongkrekic acid (isoBA) on the other hand. It is well established that these inhibitors recognise two different conformations of the carrier protein, the CATR- and BA-conformations, which exhibit different chemical, immunochemical and enzymatic reactivities. The reversible transition of the ADP/ATP carrier between the two conformations was studied by fluorometric techniques. This transconversion, which is only triggered by transportable nucleotides, is probably the same as that which occurs during the functioning of ADP/ATP transport system. The fluorometric approach, using the tryptophanyl residues of the yeast carrier as intrinsic fluorescence probes, was combined to a mutagenesis approach to elucidate the ADP/ATP transport mechanism at the molecular level. Finally, recent reports that myopathies might result from defect in ADP/ATP transport led us to develop a method to quantify the carrier protein in muscular biopsies.
authors.affiliation: UMR 314 CNRS, Département de Biologie Moléculaire et Structurale, CEA-Grenoble, France.
authors.forename: C
authors.initials: C
authors.lastname: Fiore
authors.forename: V
authors.initials: V
authors.lastname: Trézéguet
authors.forename: A
authors.initials: A
authors.lastname: Le Saux
authors.forename: P
authors.initials: P
authors.lastname: Roux
authors.forename: C
authors.initials: C
authors.lastname: Schwimmer
authors.forename: A C
authors.initials: AC
authors.lastname: Dianoux
authors.forename: F
authors.initials: F
authors.lastname: Noel
authors.forename: G J
authors.initials: GJ
authors.lastname: Lauquin
authors.forename: G
authors.initials: G
authors.lastname: Brandolin
authors.forename: P V
authors.initials: PV
authors.lastname: Vignais
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D003600:Cytosol / Q000378:metabolism; D005057:Eukaryotic Cells; D005453:Fluorescence; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017240:Mitochondrial Myopathies / Q000209:etiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases