Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides.
Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010071:Oxaloacetates / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D013386:Succinates / Q000378:metabolism
D006885:Hydroxybutyrates; D010071:Oxaloacetates; D013386:Succinates; D009243:NAD; D012430:Ruthenium Red; D009249:NADP; D000255:Adenosine Triphosphate; D001205:Ascorbic Acid; D002118:Calcium