Stimulation of ATP synthase by Ca2+ in heart mitochondria

Abstract

We have shown that Ca2+ ions within the physiological range of concentrations activate the succinate oxidation rate in rat heart mitochondrija at 28 °C, but have no effect at 37 °C. The ability of Ca2+ to stimulate only state 3 respiration at 28 °C but not the respiration in the uncoupled state confirms that the respiratory subsystem is not sensitive to Ca2+ and that the stimulatory effect of Ca2+ resides within the phosphorylation subsystem. The results of modular kinetic analysis are in line with this conclusion. Since the only component of the phosphorylation subsystem exerting an appreciable control over respiration rate in state 3 at 28 °C is ATP synthase, we conclude that Ca2+ directly stimulates ATP synthase. This effect is responsible for activation of the phosphorylation subsystem by calcium, however, it is manifested only under conditions where ATP synthase contributes to the control of respiration (at 28 °C but not at 37 °C). Keywords: heart mitochondria, calcium, oxidative phosphorylation, ATP synthase, metabolic control analysis