Theoretical studies on control of oxidative phosphorylation in muscle mitochondria at different energy demands and oxygen concentrations

The mathematical dynamic model of oxidative phosphorylation in muscle mitochondria developed previously was used to calculate the flux control coefficients of particular steps of this process in isolated mitochondria at different amounts of hexokinase and oxygen concentrations. The pattern of control was completely different under different conditions. For normoxic concentration, the main controlling steps in state 4, state 3.5 and state 3 were proton leak, ATP usage (hexokinase) and complex III, respectively. The pattern of control in state 4 was not changed at hypoxic oxygen concentration, while in state 3.5 and state 3 much of the control was shifted from other steps to cytochrome oxidase. The implications of the theoretical results obtained for the regulation of oxidative phosphorylation in intact muscle are discussed.