Translation rates of isolated liver mitochondria under conditions of hepatic mitochondrial proliferation.

The hepatic mitochondrial content is increased in rats by treatment with the hypolipidaemic drug clofibrate and by administration of the cobalamin analogue hydroxycobalamin[c-lactam] (HCCL), an inhibitor of hepatic L-methylmalonyl-CoA mutase activity. As a first step in defining the mechanisms regulating liver mitochondrial contents in these models, the current studies were designed to test the hypothesis that hepatic mitochondrial proliferation is associated with enhanced translation rates of mitochondrial DNA gene products. Incorporation of [35S]methionine and [3H]leucine into protein was quantified in mitochondria isolated from control, clofibrate- and HCCL-treated rats. Use of multiple amino acid substrate concentrations permitted the maximal rate of translation (Vmax.) to be determined independent of endogenous amino acid concentrations. The Vmax. for methionine incorporation was not different in the models evaluated (0.062, 0.057 and 0.061 pmol/min per mg of mitochondrial protein in control, clofibrate- and HCCL-treated rats respectively). Similar results were obtained for leucine incorporation when absolute fractional radiolabel incorporation rates were analysed and when conventional Lineweaver-Burk analysis was employed. These results demonstrate no change in the intrinsic capacity of mitochondrial translation in these two models of hepatic mitochondrial proliferation.