The Ca2+-binding glycoprotein as the site of metabolic regulation of mitochondrial Ca2+ movements.
A change in the redox state of pyridine nucleotides such as that evoked by addition of oxaloacetate has been shown to promote Ca2+ efflux from Ca2+ pre-loaded respiring mitochondria. An affinity-chromatography-purified antibody preparation obtained against the mitochondrial Ca2+-binding glycoprotein inhibits the phenomenon. This finding suggests that the glycoprotein is involved also in the oxaloacetate-induced Ca2+ release. This conclusion is reinforced by the finding that Ca2+-binding glycoprotein shows four sites per molecule where the pyridine nucleotides may be bound. Binding of NAD+ occurs preferentially over the others and the binding shows positive cooperativity, indicating that the glycoprotein undergoes an allosteric change upon NAD+ binding. Interestingly, in addition, NAD+ lowers the affinity of the glycoprotein for Ca2+. The effect cannot be induced by NADH. Pyridine nucleotide phosphates, NADP+ and NADPH, are essentially not bound. The results are consistent with the view that the glycoprotein is the site of regulation of Ca2+ equilibration across the mitochondrial membrane and make it possible to conclude that the effector in the phenomenon is NAD+.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008314:Malonates / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D010071:Oxaloacetates / Q000494:pharmacology; D051381:Rats
D002135:Calcium-Binding Proteins; D008314:Malonates; D010071:Oxaloacetates; D009243:NAD; D009249:NADP; D008274:Magnesium; D002118:Calcium