Calcium regulation of oxidative phosphorylation in rat skeletal muscle mitochondria.

TitleCalcium regulation of oxidative phosphorylation in rat skeletal muscle mitochondria.
Publication TypeJournal Article
Year of Publication2000
AuthorsKavanagh, NI, Ainscow, EK, Brand, MD
JournalBiochim Biophys Acta
Volume1457
Issue1-2
Pagination57-70
Date Published2000 Feb 24
ISSN0006-3002
KeywordsAnimals, Calcium, Enzyme Activation, Female, In Vitro Techniques, Ketoglutaric Acids, Mitochondria, Muscle, Muscle, Skeletal, Oxidative Phosphorylation, Oxygen Consumption, Rats, Rats, Wistar, Succinic Acid
Abstract

Activation of oxidative phosphorylation by physiological levels of calcium in mitochondria from rat skeletal muscle was analysed using top-down elasticity and regulation analysis. Oxidative phosphorylation was conceptually divided into three subsystems (substrate oxidation, proton leak and phosphorylation) connected by the membrane potential or the protonmotive force. Calcium directly activated the phosphorylation subsystem and (with sub-saturating 2-oxoglutarate) the substrate oxidation subsystem but had no effect on the proton leak kinetics. The response of mitochondria respiring on 2-oxoglutarate at two physiological concentrations of free calcium was quantified using control and regulation analysis. The partial integrated response coefficients showed that direct stimulation of substrate oxidation contributed 86% of the effect of calcium on state 3 oxygen consumption, and direct activation of the phosphorylation reactions caused 37% of the increase in phosphorylation flux. Calcium directly activated phosphorylation more strongly than substrate oxidation (78% compared to 45%) to achieve homeostasis of mitochondrial membrane potential during large increases in flux.

DOI10.1016/s0005-2728(00)00054-2
Alternate JournalBiochim. Biophys. Acta
Citation Key10.1016/s0005-2728(00)00054-2
PubMed ID10692550