Towards the molecular basis for the regulation of mitochondrial dehydrogenases by calcium ions.
In mammalian cells, increases in calcium concentration cause increases in oxidative phosphorylation. This effect is mediated by the activation of four mitochondrial dehydrogenases by calcium ions; FAD-glycerol 3-phosphate dehydrogenase, pyruvate dehydrogenase, NAD-isocitrate dehydrogenase and oxoglutarate dehydrogenase. FAD-glycerol 3-phosphate dehydrogenase, being located on the outer surface of the inner mitochondrial membrane, is exposed to fluctuations in cytoplasmic calcium concentration. The other three enzymes are located within the mitochondrial matrix. While the kinetic properties of all of these enzymes are well characterised, the molecular basis for their regulation by calcium is not. This review uses information derived from calcium binding studies, analysis of conserved calcium binding motifs and comparison of amino acid sequences from calcium sensitive and non-sensitive enzymes to discuss how the recent cloning of several subunits from the four dehydrogenases enhances our understanding of the ways in which these enzymes bind calcium. FAD-glycerol 3-phosphate dehydrogenase binds calcium ions through a domain which is part of the polypeptide chain of the enzyme. In contrast, it is possible that the calcium sensitivity of the other three dehydrogenases may involve separate calcium binding subunits.
Nichols
B J
BJ
Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.
Denton
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D017302:Annexins / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D016384:Consensus Sequence; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D017302:Annexins; D002135:Calcium-Binding Proteins; D011768:Pyruvate Dehydrogenase Complex; D005993:Glycerolphosphate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D007655:Ketoglutarate Dehydrogenase Complex; D002118:Calcium