Effect of ADP/ATP antiporter conformational state on the suppression of the nonspecific permeability of the inner mitochondrial membrane by cyclosporine A.

The influence of the conformational state of ADP/ATP antiporter on the efficiency of the inhibitory effect of cyclosporine A on the Ca2(+)-induced nonspecific permeability of the inner mitochondrial membrane has been studied. Carboxyatractiloside, the inhibitor of ADP/ATP-antiporter, was shown to prevent the cyclosporine A-induced suppression of the nonspecific permeability. The carboxyatractiloside effect was displayed only in mitochondria depleted of adenine nucleotides. Bifunctional SH reagent, phenylarsine oxide, was also able to reverse the effect of cyclosporine A. The data are consistent with the suggestion that cyclosporine A causes suppression of the nonspecific permeability due to its effect on the ADP/ATP antiporter conformation.