Direct thyroid hormone activation of mitochondria: the role of adenine nucleotide translocase.

A presumptive mitochondrial T3 receptor previously reported from this and other laboratories appears capable of accounting for the activation of liver mitochondrial oxidative phosphorylation within 30 min after iv bolus injection of nanogram doses of T3 into hypothyroid rats. The inner mitochondrial membrane carrier adenine nucleotide translocase (AdNT) catalyzes the exchange between the extra- and intramitochondrial ADP and ATP, and has been shown by measurements of flux control coefficients to exert a significant measure of control over the rate of mitochondrial oxidative phosphorylation. The activity of this carrier had been reported to be depressed below normal in hypothyroid rats and restored to normal by hormone replacement. Preparations of AdNT from beef heart mitochondria were found to exhibit high affinity, low capacity binding of [125I]T3. The findings make the mitochondrial carrier AdNT a strong candidate for the initiating site for thyroid hormone stimulation in mammalian species.