Inhibition of mitochondrial protein synthesis in regenerating rat liver stimulates mitochondrial transcription.

Partially hepatectomized rats were treated in vivo with thiamphenicol for 3 days to block mitochondrial protein synthesis. Protein synthesis, RNA synthesis and the steady-state levels of individual transcripts were measured in mitochondria in vitro in the absence of thiamphenicol. Incorporation of [35S]methionine and [3H]UTP into protein and RNA, respectively, was increased 2-3-fold in isolated mitochondria from thiamphenicol-treated animals, indicating increased rates of synthesis of both. Electrophoretic analysis of transcripts labelled with [32P]UTP suggests that synthesis of all the transcripts is increased. The steady-state concentrations of mitochondrial transcripts, measured by Northern blotting using nick-translated cloned EcoRI fragments of rat liver mtDNA, were also elevated 2-4-fold in thiamphenicol-treated animals. The data suggest that mitochondrial transcription is under control of a mitochondrial factor which, in turn, is dependent upon mitochondrial protein synthesis.