Uncoupling effect of fatty acids on heart muscle mitochondria and submitochondrial particles.
The effect of ATP/ADP-antiporter inhibitors on palmitate-induced uncoupling was studied in heart muscle mitochondria and inside-out submitochondrial particles. In both systems palmitate is found to decrease the respiration-generated membrane potential. In mitochondria, this effect is specifically abolished by carboxyatractylate (CAtr) a non-penetrating inhibitor of antiporter. In submitochondrial particles, CAtr does not abolish the palmitate-induced potential decrease. At the same time, bongkrekic acid, a penetrating inhibitor of the antiporter, suppresses the palmitate effect on the potential both in mitochondria and particles. Palmitoyl-CoA which is known to inhibit the antiporter in mitochondria as well as in particles decreases the palmitate uncoupling efficiency in both these systems. These data are in agreement with the hypothesis that the ATP/ADP-antiporter is involved in the action of free fatty acids as natural uncouplers of oxidative phosphorylation.
Dedukhova
V I
VI
Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, USSR.
Mokhova
E N
EN
Skulachev
V P
VP
Starkov
A A
AA
Arrigoni-Martelli
E
E
Bobyleva
V A
VA
D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D001865:Bongkrekic Acid / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D007700:Kinetics; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology*; D011817:Rabbits; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism*; D014475:Uncoupling Agents / Q000494:pharmacology*
D010169:Palmitic Acids; D014475:Uncoupling Agents; D001865:Bongkrekic Acid; D001278:Atractyloside; D019308:Palmitic Acid; D012967:Sodium Dodecyl Sulfate; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000226:Mitochondrial ADP, ATP Translocases; C003853:carboxyatractyloside