Some actions of thyroxine on oxidative phosphorylation

Abstract

The effects of thyroxine and three of its analogues on oxidative phosphorylation have been tested using intact mitochondria and submitochondrial particles. When intact mitochondria were maintained in isotonic sucrose, thyroxine was virtually without effect unless the mitochondria were preincubated, for a minute or more, with the reaction medium in the absence of substrate. Under such conditions phosphorylation was uncoupled from the oxidation of succinate. Intact mitochondria washed with hypotonic phosphate buffer lost oxidative activity and exhibited poorer phosphorus to oxygen ratios than aliquots of the mitochondrial suspension maintained in isotonic sucrose. Both the oxidation rate and the phosphorus to oxygen ratio of the phosphate-washed mitochondria were stimulated by thyroxine. Submitochondrial particles prepared from sonic extracts of mitochondria also showed an improvement in the rate of oxidation and in the phosphorus to oxygen ratios in the presence of thyroxine or triiodothyronine. This was true when either succinate or reduced diphosphopyridine nucleotide were used as substrates. Thyroxine concentrations from 2 to 10 times those necessary to produce increases in rate of oxidation or phosphorus to oxygen ratios uncoupled phosphorylation from oxidation in submitochondrial particles preincubated with the reaction medium for 2 min prior to the addition of thyroxine and substrate. Thyroxine appeared to have little effect on the adenosinetriphosphatase activity or on the rate of exchange of inorganic phosphate with the terminal phosphate of adenosinetriphosphate in submitochondrial particles.