Cyclosporin A-sensitive and insensitive mechanisms produce the permeability transition in mitochondria.
Cyclosporin A is a potent inhibitor of the mitochondrial permeability transition, possibly by blocking an inner membrane pore through which solute movements occur [Broekemeier et al. (1989) J. Biol. Chem. 264, 7826-7830]. The inhibitory effect of cyclosporin, however, is transient. Trifluoperazine, at concentrations which inhibit the mitochondrial phospholipase A2, also produces a transient inhibition. When both inhibitors are used together, the inhibitory effect is long lasting. These findings suggest that the transition can be caused by two overlapping and/or interactive mechanisms, one dependent on an inner membrane pore and the other on phospholipase A2.
Hormel Institute, University of Minnesota, Austin 55912.
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability; D010545:Peroxides / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D014268:Trifluoperazine / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D003524:Cyclosporins; D010545:Peroxides; D014268:Trifluoperazine; D020122:tert-Butylhydroperoxide; D010741:Phospholipases A; D054467:Phospholipases A2; D008274:Magnesium; D002118:Calcium