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 nuc lear genomes. Tfam, the activator of mammalian mitochondrial transcription, is encoded in the nucleus and its expression has been shown in in vitro st udies to be controlled by nuclear respiratory factors NRF-1 and NRF-2. In o rder to understand the physiological dependence of mitochondrial gene expre ssion, we have analyzed in rat liver, testis and brain the expression level of mitochondrial genes in parallel with those of the three transcription f actors. 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 a bundance 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, b eta 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 expressi on 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-trans criptional regulatory mechanisms for the expression of NRF-1/NRF-2 genes. ( C) 1999 Societe francaise de biochimie et biologie moleculaire / Editions s cientifiques et medicales Elsevier SAS.