Large Functional Range of Steady-State Levels of Nuclear and Mitochondrial Transcripts Coding for the Subunits of the Human Mitochondrial OXPHOS System

Abstract

We have measured, by reverse transcription and real-time quantitative PCR, the steady-state levels of the mitochondrial and nuclear transcripts encoding several subunits of the human oxidative phosphorylation (OXPHOS) system, in different normal tissues (muscle, liver, trachea, and kidney) and in cultured cells (normal fibroblasts, 143B osteosarcoma cells, 143B206 0 cells). Five mitochondrial transcripts and nine nuclear transcripts were assessed. The measured amounts of these OXPHOS transcripts in muscle samples corroborated data obtained by others using the serial analysis of gene expression (SAGE) method to appraise gene expression in the same type of tissue. Steady-state levels for all the transcripts were found to range over more than two orders of magnitude. Most of the time, the mitochondrial H-strand transcripts were present at higher levels than the nuclear transcripts. The mitochondrial L-strand transcript ND6 was usually present at a low level. Cultured 143B cells contained significantly reduced amounts of mitochondrial transcripts in comparison with the tissue samples. In 143B206 0 cells, fully depleted of mitochondrial DNA, the levels of nuclear OXPHOS transcripts were not modified in comparison with the parental cells. This observation indicated that nuclear transcription is not coordinated with mitochondrial transcription. We also observed that in the different tissues and cells, there is a transcriptional coregulation of all the investigated nuclear genes. Nuclear OXPHOS gene expression seems to be finely regulated.[The following individual kindly provided reagents, samples, or unpublished information as indicated in the paper: G. Attardi.]Through the process of oxidative phosphorylation (OXPHOS), mitochondria provide most of the ATP to eukaryotic cells. Oxidative phosphorylation corresponds to the terminal stage of substrate oxidation in mitochondria, and is catalyzed by the OXPHOS system, which functionally associates the mitochondrial respiratory chain, composed of four complexes (complexes I, II, III, and IV), and ATP synthase (complex V) for ATP synthesis. The biogenesis of all these enzymatic complexes, except complex II, requires expression of genes located at the level of both the nuclear and the mitochondrial genomes. Mechanisms that putatively coordinate the expression of these genes are poorly understood at present.

LRP130 Protein Remodels Mitochondria and Stimulates Fatty Acid Oxidation

“…One, prior reports indicate post-transcriptional mechanisms regulate many nuclearly encoded subunits. In a comparison of tissues with cultured cells, variability in OXPHOS subunits was limited mainly to mitochondrially encoded genes, changes that correlated with OXPHOS (62). Even in tissues with low expression of nuclearly encoded genes, OXPHOS still proved robust (63), provided mtDNA expression was intact.…”

mRNA degradation: an underestimated factor on steady-state transcript levels of cytochromecoxidase subunits?

“…However, this does not seem to be the case with ETC complex subunits in mammals (Duborjal et al, 2002) or in COX subunits in fish (Little et al, 2010). Another question is whether changes in levels of a multimeric enzyme require parallel changes in the synthesis of protein and mRNA for each subunit.…”

Activity Increase in Respiratory Chain Complexes by Rubella Virus with Marginal Induction of Oxidative Stress

“…They show different activity rates among each other (Fig. 1B) and also tissue-specific activity rates and expression levels (38). Each subunit of the RC complexes differs in its ability to relate its protein expression level to its enzymatic activity (39).…”