Cyclosporine A inhibits mitochondrial pyridine nucleotide hydrolysis and calcium release.

Mitochondria participate in the maintenance of cellular Ca2+ homeostasis. Here we show that the immunosuppressive drug cyclosporine A at low concentrations inhibits release but not uptake of Ca2+ by mitochondria. Prevention of Ca2+ release is due to inhibition of intramitochondrial enzymatic hydrolysis of NAD to ADP-ribose and nicotinamide. These findings suggest a mechanism by which cyclosporine A interferes with cellular Ca2+ homeostasis, and may be related to the immunosuppressive and cytotoxic properties of the drug.