Thyroxine stimulates phosphatidylglycerolphosphate synthase activity in rat heart mitochondria

The effect of administration of exogenous thyroxine on mitochondrial phosphatidylglycerol content and biosynthesis was investigated in rat heart ventricles. Rats were treated for 5 consecutive days with thyroxine (250 mg/kg body weight) and on the sixth day after an overnight fast the mass of ventricular mitochondrial phosphatidylglycerol and cardiolipin content were determined. Saline-treated animals served as controls. Thyroxine treatment did not affect body weight but increased heart weight 30% compared with controls. In addition, the ratio of heart weight/body weight (x 1000) was increased from 0.69 in controls to 0.89 in thyroxine-treated rats consistent with this model. Thyroxine-treatment resulted in a 34% increase (P < 0.05) in phosphatidylglycerol and a 23% increase (P < 0.05) in cardiolipin content in ventricular mitochondrial fractions compared with controls. The mechanism for the increase in ventricular mitochondrial phosphatidylglycerol was investigated. Phosphatidic acid:cytidine-5'-triphosphate-1,2-diacylglycerol cytidylyltransferase and phosphatidylglycerolphosphate phosphatase activities were unaltered in the ventricular mitochondria of thyroxine-treated rats. In contrast, phosphatidylglycerolphosphate synthase activity was increased 3.5-fold (P < 0.05) in these mitochondrial fractions compared with controls. As a control for the effectiveness of thyroxine on mitochondria, cardiolipin synthase activity was determined. A 2.8-fold increase (P < 0.05) in cardiolipin synthase activity was observed in ventricular mitochondrial fractions of thyroxine-treated rats compared with controls. We postulate that thyroxine-treatment of rats produces an increase in the pool size of ventricular mitochondrial phosphatidylglycerol and that the mechanism is an increase in phosphatidylglycerolphosphate synthase activity.