Fatty acid-induced Ca(2+)-dependent uncoupling and activation of external pathway of NADH oxidation are coupled to cyclosporin A-sensitive mitochondrial permeability transition.
Permeabilization of inner mitochondrial membrane by palmitic acid in the presence of Ca2+ (cyclosporin A-sensitive stimulation of respiration, decrease of delta psi and high amplitude swelling) is accompanied by activation of the external pathway of NADH oxidation in liver mitochondria. The "pore"-sealing agents (cyclosporin A, Mg2+ with ADP, and L-carnitine with ATP) are equally effective in preventing the induction of external pathway of NADH oxidation by Ca2+ with palmitate. However, activities of these agents are different in respect to recoupling of permeabilized mitochondria. Participation of cyclosporin A-sensitive "pore" in the fatty acid- and Ca(2+)-dependent induction of external pathway of NADH oxidation and in Ca(2+)-dependent uncoupling is discussed.
Starkov
A A
AA
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Markova
O V
OV
Mokhova
E N
EN
Arrigoni-Martelli
E
E
Bobyleva
V A
VA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002331:Carnitine / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D051381:Rats
D010169:Palmitic Acids; D009243:NAD; D019308:Palmitic Acid; D000244:Adenosine Diphosphate; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D008274:Magnesium; D002331:Carnitine; D002118:Calcium