Molecular and Cellular Biochemistry

, Volume 149, Issue 1, pp 203–212

Towards the molecular basis for the regulation of mitochondrial dehydrogenases by calcium ions

  • Benjamin J. Nichols
  • Richard M. Denton
Article

DOI: 10.1007/BF01076578

Cite this article as:
Nichols, B.J. & Denton, R.M. Mol Cell Biochem (1995) 149: 203. doi:10.1007/BF01076578

Abstract

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 dehydrogenases may involve separate calcium binding subunits.

Key words

calciummitochondriaFAD-glycerol 3-phosphate dehydrogenasepyruvate dehydrogenaseoxoglutarate dehydrogenaseisocitrate dehydrogenase

Abbreviations

GPDH

glycerol 3-phosphate dehydrogenase

PDH

pyruvate dehydrogenase

ICDH

isocitrate dehydrogenase

OGDH

oxoglutarate dehydrogenase

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Benjamin J. Nichols
    • 1
  • Richard M. Denton
    • 1
  1. 1.Department of Biochemistry, School of Medical SciencesUniversity of BristolBristolUK