Biogenesis of mitochondria involves the expression of genes located on nuclear 
chromosomes as well as on mitochondrial DNA. We studied the coordination of the 
two genomes by measuring transcript levels for nuclear (IV, Va, and VIc) and 
mitochondrial (II and III) subunits of cytochrome-c oxidase after altering the 
mitochondrial content of rat muscle and liver by altering the thyroid state of 
the animals. Tissue levels of these mRNAs were generally decreased in 
hypothyroid animals and were up-regulated again after thyroid hormone (T3) 
treatment. However, significant increases in the levels of all nuclear 
transcripts were observed in the liver 24 h after T3 treatment, but were delayed 
or remained unaltered (VIc) in muscle. In contrast, levels of mitochondrial 
transcripts were elevated early in muscle and late in liver. The abundance of 
the corresponding polypeptides, which were analyzed by immunoblotting, changed 
in direction and magnitude according to the changes in their mRNAs, indicating 
pretranslational control. We conclude that the two genomes are regulated by T3 
not through a common coordinating mechanism, but via two separate pathways, 
which respond to T3 with tissue-specific kinetics. S1-nuclease protection 
analysis showed that probably only one transcript for subunit VIc is present in 
both tissues, thus excluding the possibility that the tissue-specific response 
is due to the expression of two isogenes. The abundance of mitochondrial DNA was 
unaltered despite the observed changes in mitochondrial transcripts, indicating 
that mitochondrial gene expression is regulated by transcriptional mechanisms 
and not by gene dosage as has been postulated by others.