The Ca2+-Binding Glycoprotein as the Site of Metabolic Regulation of Mitochondrial Ca2+ Movements

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Abstract
A change in the redox state of pyridine nucleotides such as that evoked by addition of oxaloacetate promoted Ca2+ efflux from Ca2+ pre-loaded respiring rat liver mitochondria. An affinity-chromatography-purified antibody preparation obtained against the mitochondrial Ca2+-binding glycoprotein inhibits the phenomenon. The glycoprotein apparently is involved also in the oxaloacetate-induced Ca2+ release. This conclusion is reinforced by the finding that Ca2+-binding glycoprotein shows 4 sites/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. 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 glycoprotein apparently is the site of regulation of Ca2+ equilibration across the mitochondrial membrane and the effector in the phenomenon is NAD+. Rat liver mitochondria are known to transport Ca2+ actively in response to respiration or ATP hydrolysis.