Open AccessThe Ca 2+ ‐Binding Glycoprotein as the Site of Metabolic Regulation of Mitochondrial Ca 2+ Movements
Author(s) -
PANFILI Enrico,
SOTTOCASA Gian Luigi,
SANDRI Gabriella,
LIUT Gianfranco
Publication year - 1980
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1980.tb04490.x
Subject(s) - nad+ kinase , allosteric regulation , glycoprotein , cooperativity , biochemistry , binding site , nucleotide , mitochondrion , chemistry , cooperative binding , biology , receptor , enzyme , gene
A change in the redox state of pyridine nucleotides such as that evoked by addition of oxalo‐acetate has been shown to promote Ca 2+ efflux from Ca 2+ pre‐loaded respiring mitochondria. An affinity‐chromatography‐purified antibody preparation obtained against the mitochondrial Ca 2+ ‐binding glycoprotein inhibits the phenomenon. This finding suggests that the glycoprotein is involved also in the oxaloacetate‐induced Ca 2+ release. This conclusion is reinforced by the finding that Ca 2+ ‐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 Ca 2+ . 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 Ca 2+ equilibration across the mitochondrial membrane and make it possible to conclude that the effector in the phenomenon is NAD + .