[Inhibitors of the ADP/ATP antiporter induce two Ca2+-dependent uncoupling systems in rat liver mitochondria].
Effect of an ADP/ATP antiporter inhibitor carboxyatractylate on permeability of inner mitochondrial membrane was studied. Carboxyatractylate induced two uncoupling systems: Ca(2+)-dependent pore and another system which was sensitive to an inhibitor of calcium uniporter ruthenium red (apparently, Ca(2+)-recycle). Extent of Ca(2+)-recycle induction correlates with a fraction of mitochondrial population which underwent permeabilization; inhibition of permeabilization by cyclosporin A prevents induction of the recycle. Thus, induction of Ca(2+)-dependent pore is direct consequence of carboxyatractylate binding to mitochondria whereas induction of Ca(2+)-recycle is indirect. Both uncoupling systems are induced by carboxyatractylate concentrations which are specific for ADP/ATP antiporter. The data suggest that the antiporter can directly participate in the formation of Ca(2+)-dependent pore in inner mitochondrial membrane.
Mikhaĭlova
L M
LM
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore 21201, USA.
Kushnareva
Iu E
IuE
Andreev
A Iu
AIu
D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D007425:Intracellular Membranes / Q000187:drug effects; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors*; D024101:Mitochondrial Proteins; D010539:Permeability / Q000187:drug effects; D051381:Rats; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; D001278:Atractyloside; D000226:Mitochondrial ADP, ATP Translocases; C003853:carboxyatractyloside; D002118:Calcium