THE ROLE OF CREATINE-KINASE IN INHIBITION OF MITOCHONDRIAL PERMEABILITY TRANSITION

Cyclosporin A sensitive smelling of mitochondria isolated from control mouse livers and from the livers of transgenic mice expressing human ubiquitous mitochondrial creatine kinase occurred in the presence of b oth 40 mu M calcium and 5 mu M atractyloside which was accompanied by a 2.5-fold increase over state 4 respiration rates, Creatine and cyclo creatine inhibited the latter only in transgenic liver mitochondria, P rotein complexes isolated from detergent solubilised rat brain extract s, containing octameric mitochondrial creatine kinase, porin and the a denine nucleotide translocator, were reconstituted into malate loaded lipid vesicles, Dimerisation of creatine kinase in the complexes and e xposure of the reconstituted complexes to >200 mu M calcium induced a cyclosporin A sensitive malate release, No malate release occurred wit h complexes containing octameric creatine kinase under the same condit ions. (C) 1997 Federation of European Biochemical Societies.