Dissociation between mitochondria calcium ion release and pyridine nucleotide oxidation.
In the presence of phosphate, both acetoacetate and palmitoyl-coenzyme A induce pyridine nucleotide oxidation, swelling of mitochondria, and Ca2+ release. However, when mitochondria accumulate Ca2+ in the presence of lactate, neither acetoacetate nor palmitoyl-CoA addition results in Ca2+ release and no swelling is observed. If ruthenium red is added prior to these releasing agents, a 10-fold greater rate of Ca2+ efflux is observed when phosphate is present compared to lactate alone. Although acetoacetate produces significant oxidation of NADH in the lactate-supplemented medium, no Ca2+ release occurs. In the lactate medium, no oxidation of pyridine nucleotide was seen following palmitoyl-CoA addition. Lactate-supported Ca2+ accumulation (+/- N-ethylmaleimide) produces a transient respiratory stimulation associated with active Ca2+ uptake. Addition of phosphate to Ca2+-loaded mitochondria (lactate medium) promotes respiratory stimulation and Ca2+ efflux upon addition of acetoacetate or palmitoyl-CoA. When N-ethylmaleimide is present to inhibit the phosphate-hydroxyl exchange, no efflux of Ca2+ occurs after addition of phosphate and acetoacetate or phosphate and palmitoyl-CoA. The ionophore, A23187, produces Ca2+ release from mitochondria in either lactate (+/- N-ethylmaleimide) or phosphate medium. These results suggest that activation by the reduction state of mitochondrial pyridine nucleotides but may also depend upon the nature of the accompanying anion, as well as membrane permeability alterations.
D000090:Acetoacetates / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D051381:Rats
D000090:Acetoacetates; D009243:NAD; D010171:Palmitoyl Coenzyme A; D009249:NADP; D002118:Calcium