Role of calcium in respiratory control

Ca2+ ions activate four mitochondrial enzymes (viz. glycerol 3-phosphate dehydrogenase, pyruvate dehydrogenase phosphatase, NAD-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase) that are involved in substrate dehydrogenation and production of NADH as a substrate for oxidative phosphorylation. As cytosol Ca2+, and presumably mitochondrial Ca2+, concentrations are raised during muscle contraction, this is thought to provide a mechanism whereby the activity of oxidative phosphorylation is raised in working muscle without the necessity of unacceptably large decreases in adenine nucleotide phosphorylation potential. These ideas are explored in this article, with particular reference to the activation of pyruvate dehydrogenase in cardiac and skeletal muscle preparations and its dependence upon both cytosolic and intramitochondrial Ca2+ ion concentrations.