RESEALING OF THE PERMEABILITY TRANSITION PORE BY CYCLOSPORINE-A - THEROLE OF MG2-NUCLEOTIDES, AND THE CONFORMATION OF ATP(, ADENINE)ADP-ANTIPORTER/

Effects of ADP and Mg2+ on the ability of cyclosporin A to reseal mito chondria permeabilized by Ca2+ and P-i were studied. Cyclosporin A was completely ineffective if ADP and Mg2+ were not included in the incub ation medium. Both ADP and Mg2+ at high concentrations potentiated the effect of cyclosporin A and prevented it from reversal by carboxyatra ctylate. Data on the influence of different concentrations of ADP and Mg2+ on the resealing efficiency of cyclasporin A led us to the assump tion that the ADP-Mg2+ complex, but not ADP or Mg2+ separately, is a t rue effector modulating the permeability transition pore state. We com pared the potencies of the non-metabolizable analogs of adenine nucleo tides ADP-S-3 and ATP-S to potentiate the resealing action of cyclospo rin on mitochondria permeabilized by loading with different Ca2+ conce ntrations to that of ADP. ATP-S was ineffective if the pore was induce d by high concentrations of Ca2+. The results are discussed in terms o f hypothesized direct involvement of ADP/ATP-antiporter in the regulat ion of mitochondrial inner membrane permeability transition pore state .