title: Cyclosporine A inhibits mitochondrial pyridine nucleotide hydrolysis and calcium release.
abstract: 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.
authors.affiliation: Laboratory of Biochemistry I, Swiss Federal Institute of Technology, Zürich.
authors.forename: C
authors.initials: C
authors.lastname: Richter
authors.forename: M
authors.initials: M
authors.lastname: Theus
authors.forename: J
authors.initials: J
authors.lastname: Schlegel
mesh_terms: 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
chemical_list: D003524:Cyclosporins; D010545:Peroxides; D009243:NAD; D000496:Alloxan; D020122:tert-Butylhydroperoxide; D002118:Calcium