Expression of mitochondrial genes and of the transcription factors involved in the biogenesis of mitochondria Tfam, NRF-1 and NRF-2, in rat liver, testis and brain.

Mitochondrial function requires genes encoded in both mitochondrial and nuclear genomes. Tfam, the activator of mammalian mitochondrial transcription, is encoded in the nucleus and its expression has been shown in in vitro studies to be controlled by nuclear respiratory factors NRF-1 and NRF-2. In order to understand the physiological dependence of mitochondrial gene expression, we have analyzed in rat liver, testis and brain the expression level of mitochondrial genes in parallel with those of the three transcription factors. We found that: a) Tfam expression is down-regulated in rat testis, both at the protein and transcript level. The three-fold reduction in the abundance of Tfam protein in rat testis does not result in low steady-state levels of mitochondrial gene transcripts, suggesting that Tfam is in excess and does not limit transcription in vivo; and b) NRF-1 and NRF-2 (alpha, beta and gamma subunits) mRNAs were analyzed by Northern blotting; for each mRNA, several transcripts were observed as well as tissue-specific patterns of expression. The mRNA steady-state levels of NRF-1 and NRF-2 were higher in testis than in liver or brain. These data suggest that the low expression level of Tfam found in testis is not due to decreased NRF-1 and/or NRF-2 expression and further suggest the existence of tissue-specific post-transcriptional regulatory mechanisms for the expression of NRF-1/NRF-2 genes.