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Mitochondrial respiratory function requires the expression of genes both from the mitochondrial and nuclear genomes. Nuclear respiratory factor 2 (NRF-2) is a transcription factor required for the expression of several nuclear-encoded mitochondrial proteins, including the specific mitochondrial transcription factor Tfam. This makes NRF-2 a likely candidate to coordinate expression of mitochondrial components. NRF-2 is a multisubunit complex of which the α subunit binds DNA and the β subunit enhances this binding, respectively. We have analysed in vivo the expression patterns of NRF-2 subunits both at the mRNA and protein level, in three rat tissues, liver, testis, and brain. In contrast with Tfam or the 'housekeeping' β-actin expressions in which a parallel gradient was observed, no correlation was found between NRF-2 mRNAs and proteins levels, thus suggesting post-transcriptional regulation. © 2000 Société française de biochimie et biologie moléculaire /Éditions scientifiques et médicales Elsevier SAS., This work was supported by grant PM97-0066 from the Dirección General de Enseñanza Superior e Investigación Científica (Ministerio de Educación y Cultura, Spain). H.E. was supported by a collaboration contract between CSIC and Biotools SA.

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 (α, β and γ 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., This work was supported by grants, APC 97-0005 (C.G.V.) and PB7-0066 (A.R.P. and C.G.V.) from the Dirección General de Investigación Científica y Técnica (Ministerio de Educación y Cultura, Spain).