Transcript levels for nuclear-encoded mammalian mitochondrial respiratory-chain components are regulated by thyroid hormone in an uncoordinated fashion.

Thyroid hormone is one of the few known physiological regulators of mammalian mitochondrial biogenesis. Although it exerts a global effect on biogenesis, it does so by regulating the expression of a limited number of unidentified mitochondrial proteins. We have investigated these hormone-regulated proteins in rat liver. Hormone injection induced a 30-fold increase in the levels of cytochrome-c1 mRNA after 3 d. In addition, the mRNA for the growth-activated adenine-nucleotide translocator, ANT2, was increased 13-fold and that for the ATPase N,N'-dicyclohexylcarbodiimide-binding protein increased 4-5-fold. Mitochondrial transcripts of cytochrome-oxidase subunit I also increased. No changes were found in the mRNA levels for the F1-ATPase beta-subunit or cytochrome oxidase IV. A single low dose of triiodothyronine induces rapid increases in cytochrome-c1 and ANT2 mRNA species which parallel changes in the activity of the hormone-responsive malic enzyme, but are earlier than other mitochondrial biogenetic events. These data strengthen the view that thyroid hormone regulates synthesis of specific components within each respiratory-chain complex and that these products apparently play key roles in inner-membrane biogenesis and assembly. The significance of ANT2 induction is also discussed with respect to the rapid respiratory response induced by thyroid hormone.