CYCLOSPORINE-A INHIBITS ATP NET UPTAKE OF RAT-KIDNEY MITOCHONDRIA

The adenine nucleotide content of mitochondria varies at several physiological and pathological situations. Both net transport and intramitochondrial catabolism of adenine nucleotides has been suggested to be responsible for these changes. Here, the influence of cyclosporine A on the ATP net uptake of isolated rat kidney mitochondria was examined. The ATP net uptake of mitochondria depleted of matrix adenine nucleotides by pyrophosphate treatment was inhibited by cyclosporine A showing a I50 value of about 4 nmol/mg mitochondrial protein. Because intramitochondrial adenine nucleotide content is important for several mitochondrial functions such as oxidative phosphorylation, Ca2+ homoeostasis and mitochondrial biogenesis, it is concluded that the inhibition of adenine nucleotide net transport and a decrease of adenine nucleotide content may be involved in the immunosuppressive and nephrotoxic effects of cyclosporine A.