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.
Richter
C
C
Laboratory of Biochemistry I, Swiss Federal Institute of Technology, Zürich.
Theus
M
M
Schlegel
J
J
D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D006868:Hydrolysis; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D020122:tert-Butylhydroperoxide
D003524:Cyclosporins; D010545:Peroxides; D009243:NAD; D000496:Alloxan; D020122:tert-Butylhydroperoxide; D002118:Calcium