Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein.
Possible involvement of the ATP/ADP antiporter and uncoupling protein (UCP) in thermoregulatory uncoupling of oxidative phosphorylation in heart muscle has been studied. To this end, effects of carboxyatractylate (cAtr) and GDP, specific inhibitors of the antiporter and UCP, on the membrane potential of the oligomycin-treated mitochondria from cold-exposed (6 degrees C, 48 h) and control rats have been measured. It is found that cAtr increases the membrane potential level in both cold-exposed and non-exposed groups, the effect being strongly enhanced by cooling. As for GDP, it is effective only in mitochondria from the cold-exposed rats. In these mitochondria, the coupling effect of GDP is smaller than that of cAtr. CDP, which does not interact with UCP, is without any influence on membrane potential. The cold exposure is found to increase the uncoupling efficiency of added natural (palmitate) or artificial (SF6847) uncouplers, the increase being cAtr- and GDP-sensitive in the case of palmitate. The fatty acid-free bovine serum albumin enhances delta psi in both cold-exposed and control groups, the effect being much larger in the former case. It is concluded that in heart muscle mitochondria the ATP/ADP antiporter is responsible for the 'mild uncoupling' under normal conditions and for major portion of the thermoregulatory uncoupling in the cold whereas the rest of thermoregulatory uncoupling is served by UCP (presumably by UCP2 since the UCP2 mRNA level is shown to strongly increase in rat heart muscle under the cold exposure conditions used).
Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
R A
RA
Simonyan
V P
VP
Skulachev
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D003080:Cold Temperature; D006153:Guanosine Diphosphate / Q000494:pharmacology; D007473:Ion Channels; D008314:Malonates / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D019802:Succinic Acid / Q000378:metabolism; D013772:Tetramethylphenylenediamine / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008314:Malonates; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009570:Nitriles; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D006153:Guanosine Diphosphate; D001278:Atractyloside; D012710:Serum Albumin, Bovine; C001784:SF 6847; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C030290:malonic acid; D019802:Succinic Acid; D013772:Tetramethylphenylenediamine; C003853:carboxyatractyloside