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.