Calcium regulation of oxidative phosphorylation in rat skeletal muscle mitochondria

• Published in: Biochimica et biophysica acta Vol. 1457; no. 1; pp. 57 - 70
• Main Authors: Kavanagh, N.Irene, Ainscow, Edward K., Brand, Martin D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 24.02.2000
• Subjects: Animals; Calcium; Calcium - pharmacology; Control analysis; Enzyme Activation - drug effects; Female; In Vitro Techniques; Ketoglutaric Acids - metabolism; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - metabolism; Muscle mitochondria; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Oxidative phosphorylation; Oxidative Phosphorylation - drug effects; Oxygen Consumption; Rats; Rats, Wistar; Regulation analysis; Succinic Acid - metabolism; Top-down elasticity analysis; NTA, nitrilotriacetic acid; Regulation analysis; Calcium; IR, integrated response coefficient; Control analysis; TPMP, triphenylmethylphosphonium; DMO, dimethyloxazolidine-2,4-dione; Δ p, protonmotive force; Muscle mitochondria; Top-down elasticity analysis; C, control coefficient; Oxidative phosphorylation; Δψ, mitochondrial membrane potential; ε, elasticity; ΔpH, mitochondrial pH gradient; J S, J L, J P, fluxes through the substrate oxidation ( J S), proton leak ( J L), and phosphorylation ( J P) subsystems; FCCP, p-trifluoromethoxycarbonylcyanide phenylhydrazone
• ISSN: 0005-2728; 0006-3002; 1879-2650
• DOI: 10.1016/S0005-2728(00)00054-2

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.