Control of Respiration and ATP Hydrolysis in Uncoupled Mitochondria

The determination of the regulatory steps of oxidative phosphorylation has been a very controversial problem for several years. However, by using the theory of metabolic control (for reviews see Westerhoff et al., 1984a; Kacser and Porteous, 1987), it has recently been established (Groen et al. 1982; Bohnensack et al., 1982; Doussiere et al., 1984; Baggetto et al., 1984; Moreno-Sanchez, 1985b) that the control of oxidative phosphorylation at near saturating oxidizable substrate concentrations is mainly shared by the ATP/ADP carrier, the ATP synthase, the dicarboxylate carrier, the cytochrome b-c1 complex and the cytochrome oxidase. As this pathway consists of oxidative and synthetic (ADP-ATP transport and ATP synthesis) reactions it was the purpose of this work to get a better understanding of the regulatory properties of each subsystem by studying both the control of respiration in uncoupled mitochondria and submitochondrial particles and the control of ATP hydrolysis in uncoupled mitochondria.