THYROID HORMONE-INDUCED EXPRESSION OF THE ADP ATP CARRIER AND ITS EFFECT ON FATTY ACID-INDUCED UNCOUPLING OF OXIDATIVE-PHOSPHORYLATION/

Liver mitochondria from rats made hypothyroid by administration of 2-m ercapto-1-methylimidazole were less sensitive to the uncoupling effect of myristic acid, as measured by the increase of resting state respir ation, than mitochondria from euthyroid animals, whereas subsequent ad ministration to the animals of triiodothyronine ('hyperthyroidism') re sulted in an increased uncoupling action of myristate. 'Hyperthyroidis m' also resulted in doubling of the carboxyatractyloside-sensitive por tion of the myristate-stimulated respiration. Parallel to this was a t wofold increase of the mitochondrial content of the ADP/ATP carrier pr otein and an over threefold increase of its activity. The uncoupling e ffect of phytanic acid was less sensitive to carboxyatractyloside and was increased in the hyperthyroid state to a smaller extent than in th e case of myristate. These results provide further support to the thes is [Skulachev, V.P., FEBS Lett. 294 (1991) 158-162] that the ADP/ATP c arrier is involved in the mechanism of the uncoupling effect of long-c hain fatty acids. (C) 1997 Federation of European Biochemical Societie s.