title: The involvement of cyclosporin A binding proteins in regulating and uncoupling mitochondrial energy transduction.
abstract: The uncoupling of mitochondrial energy transduction by excess Ca2+ may be a factor in the pathogenesis of tissue injury brought about by energy deprivation, for example, in ischaemia. In isolated mitochondria the lesion appears as a large, 20 A, pore in the inner membrane. The pore is blocked potently by the immunosuppressant cyclosporin A. Cyclosporin A also markedly retards collapse of the mitochondrial inner membrane potential in energy-deprived (respiration-inhibited) cardiomyocytes as judged by changes in rhodamine 123 fluorescence, and prolongs cell viability. A potential mitochondrial target for cyclosporin A is the matrix protein cyclophilin. Purified cyclophilin activates the respiratory chain of submitochondrial particles. This might reflect not only a physiological function of this protein, but also a component involved in the generation of the 20 A pore under pathological conditions.
authors.affiliation: Department of Biochemistry and Molecular Biology, University College London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Crompton
authors.forename: O
authors.initials: O
authors.lastname: McGuinness
authors.forename: W
authors.initials: W
authors.lastname: Nazareth
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000378:metabolism*; D004734:Energy Metabolism; D008928:Mitochondria / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D011971:Receptors, Immunologic; C028752:cyclosporin receptor; D016572:Cyclosporine; D002118:Calcium