The mechanism of palmitoyl-CoA inhibition of Ca2+ uptake in liver and heart mitochondria.
The mechanism by which palmitoyl-CoA inhibits Ca2+ uptake in liver and heart mitochondria was examined. At a given concentration of palmitoyl-CoA, the extent of inhibition is inversely related to the concentration of the respiratory substrate succinate. Palmitoyl-CoA inhibition of uncoupler-stimulated respiration and respiration stimulated by ionophore-A23187-induced Ca2+ cycling is also relieved by high succinate concentrations. These effects of palmitoyl-CoA and succinate concentration are distinct from the increase in inner-membrane permeability, which can be produced by palmitoyl-CoA and Ca2+ [Beatrice, Palmer & Pfeiffer (1980) J. Biol. Chem. 255, 8663-8671]. The apparent K0.5 of the mitochondrial Ca2+ pump is not altered by palmitoyl-CoA. No or negligible effects of palmitoyl-CoA on the Ca2+-uptake rate are observed when ascorbate replaces succinate as an energy source. These findings, together with the known activity of palmitoyl-CoA as a competitive inhibitor of the dicarboxylate carrier [Morel, Lauquin, Lunardi, Duszynski & Vignais (1974) FEBS Lett. 39, 133-138], indicate that palmitoyl-CoA inhibits energy-linked Ca2+ transport by limiting the rate of electron transport through limitation of succinate entry into the mitochondria rather than by directly inhibiting the Ca2+ carrier.
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology; D051381:Rats; D013386:Succinates / Q000494:pharmacology
D000214:Acyl Coenzyme A; D010710:Phosphates; D013386:Succinates; D010171:Palmitoyl Coenzyme A; D002118:Calcium