Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding

Changes in the kinetics and regulation of oxidative phosphorylation were ch aracterized in isolated rat liver mitochondria after 2 months of ethanol co nsumption. Mitochondrial energy metabolism was conceptually divided into th ree groups of reactions, either producing protonmotive force (Delta p) (the respiratory subsystem) or consuming it (the phosphorylation subsystem and the proton leak), Manifestation of ethanol-induced mitochondrial malfunctio ning of the respiratory subsystem was observed with various substrates; the respiration rate in State 3 was inhibited by 27 +/- 4% with succinate plus amytal, by 20 +/- 4% with glutamate pins malate, and by 17+/-2% with N,N,N ',N'-tetramethyl-p-phenylencdiamine/ascorbate. The inhibition of the respir atory activity correlated with the lower activities of cytochrome c oxidase , the bc(1) complex, and the ATP synthase in mitochondria of ethanol-fed ra ts. The block of reactions consuming the Delta p to produce ATP (the phosph orylating subsystem) was suppressed after 2 months of ethanol feeding, wher eas the mitochondrial proton leak was not affected. The contributions of De lta p supply (the respiratory subsystem) and Delta p demand (the phosphoryl ation and the proton leak) to the control of the respiratory flux were quan tified as the control coefficients of these subsystems. In State 3, the dis tribution of control exerted by different reaction blocks over respiratory flux was not significantly affected by ethanol diet, despite the marked cha nges in the kinetics of individual functional units of mitochondrial oxidat ive phosphorylation. This suggests the operation of compensatory mechanisms , when control redistributes among the different components within the same subsystem.