THE MITOCHONDRIAL ADP ATP CARRIER - STRUCTURAL, PHYSIOLOGICAL AND PATHOLOGICAL ASPECTS/

Under the conditions of oxidative phosphorylation, the mitochondrial A DP/ATP carrier catalyses the one to one exchange of cytosolic ADP agai nst matrix ATP across the inner mitochondrial membrane. The ADP/ATP tr ansport system can be blocked very specifically by two families of inh ibitors: atractyloside (ATR) and carboxyatractyloside (CATR) on one ha nd, and bongkrekic acid (BA) and isobongkrekic acid (isoBA) on the oth er hand. It is well established that these inhibitors recognise two di fferent conformations of the carrier protein, the CATR-and BA-conforma tions, 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 tr ansconversion, which is only triggered by transportable nucleotides. i s probably the same as that which occurs during the functioning of ADP /ATP transport system. The fluorometric approach, using the tryptophan yl 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 myopat hies might result from defect in ADP/ATP transport led us to develop a method to quantify the carrier protein in muscular biopsies. ((C) Soc iete francaise de biochimie et biologie moleculaire/Elsevier, Paris).