Inhibitors of the ADP/ATP antiporter induce two Ca2+-dependent uncoupling systems in rat liver mitochondria

Mikhaĭlova, L.M.; Kushnareva, I.E.; Andreev, A.I.

Biokhimiia 61(7): 1270-1278

1996


ISSN/ISBN: 0320-9725
PMID: 9035739
Document Number: 463366
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.

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