title: The role of Ca2+ ions in the regulation of intramitochondrial metabolism and energy production in rat heart.
abstract: In the heart and other mammalian tissues, there are three exclusively intramitochondrial dehydrogenases that occupy key regulatory sites in oxidative metabolism which can be activated by increases in Ca2+ in the approximate range 0.05-5 microM; they are the pyruvate, NAD+-isocitrate and 2-oxoglutarate dehydrogenases. Activation of these enzymes can be demonstrated within intact mitochondria, incubated under expected physiological conditions, when the extramitochondrial concentration of Ca+ is raised within the expected physiological range. Recent studies with fura-2-loaded mitochondria have established that matrix Ca2+ is indeed in the 0.02-2 microM range as the enzymes are activated. There is now good evidence that in the rat heart, increases in cytoplasmic [Ca2+] caused by various inotropic agents result in increases in intramitochondrial Ca2+ and activation of these dehydrogenases. It is argued therefore that matrix Ca2+ may thus be a key regulator of oxidative phosphorylation under such circumstances. The major advantage of such a mechanism of dehydrogenase-based control of this process would be to the energy homeostasis of the cell by allowing stimulated ATP production without the need to decrease the ATP/ADP ratio. Therefore it is also proposed that the major function of the mitochondrial Ca2+-transport system is to regulate matrix Ca2+, and that the ability of mitochondria to buffer the extramitochondrial concentration of Ca2+ may thus only be reserved for pathophysiological conditions of abnormal sarcolemmal Ca2+ influx as perhaps may occur in ischaemia-reperfusion.
authors.affiliation: Department of Biochemistry, University of Leeds, UK.
authors.forename: J G
authors.initials: JG
authors.lastname: McCormack
authors.forename: R M
authors.initials: RM
authors.lastname: Denton
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004734:Energy Metabolism; D004789:Enzyme Activation; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D007658:Ketone Oxidoreductases; D007655:Ketoglutarate Dehydrogenase Complex; D002118:Calcium