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-mercapto-1-methylimidazole were less sensitive to the uncoupling effect of myristic acid, as measured by the increase of resting state respiration, than mitochondria from euthyroid animals, whereas subsequent administration to the animals of triiodothyronine ('hyperthyroidism') resulted in an increased uncoupling action of myristate. 'Hyperthyroidism' also resulted in doubling of the carboxyatractyloside-sensitive portion of the myristate-stimulated respiration. Parallel to this was a twofold increase of the mitochondrial content of the ADP/ATP carrier protein and an over threefold increase of its activity. The uncoupling effect of phytanic acid was less sensitive to carboxyatractyloside and was increased in the hyperthyroid state to a smaller extent than in the case of myristate. These results provide further support to the thesis [Skulachev, V.P., FEBS Lett. 294 (1991) 158-162] that the ADP/ATP carrier is involved in the mechanism of the uncoupling effect of long-chain fatty acids.