Abstract

BackgroundThe mitochondrial oxidative phosphorylation (OXPHOS) is critical for energy (ATP) production in eukaryotic cells. It was previously shown that genes coding for mitochondrial proteins involved in energy production co-express at the RNA level. Because the OXPHOS enzymes are multimeric complexes, we tested the hypothesis that genes coding for components of specific complexes are also co-regulated at the transcriptional level, and share common regulatory elements in their promoters.ResultsWe observed for the first time that, not only OXPHOS genes as a group co-express, but there is a co-expression of genes within each of the five OXPHOS enzyme complexes, showing a higher degree of complexity in gene co-regulation. In silico analysis of homologous promoter sequences in mammals identified the likely core promoter elements for most genes encoding OXPHOS subunits/assembly factors. The results included a significant abundance of previously identified sites (e.g. NRF1, NRF2, ERRA and YY1), as well as several sites that had not been previously detected. Although we identified patterns that correlated to OXPHOS gene expression, we did not detect an OXPHOS complex-specific arrangement of transcription factor binding sites within the core promoter that could explain the tight co-expression of these functionally related genes.ConclusionThis study mapped the core promoters of most OXPHOS related genes and provided an example of gene expression regulation based on the final protein arrangement within a linear metabolic pathway.

Highlights

  • The mitochondrial oxidative phosphorylation (OXPHOS) is critical for energy (ATP) production in eukaryotic cells

  • Most OXPHOS genes are co-expressed across humans and mouse normal tissues From various genome wide expression studies, a significant group of OXPHOS genes appears to be co-expressed under various physiological conditions in several species

  • Using custom-designed whole-genome gene expression arrays from panels of mRNAs derived from 79 human and 61 mouse tissues and cell types performed in duplicates, this compendium evaluates the relative expression of 44,775 human and 36,182 mouse transcripts [28]

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Summary

Introduction

The mitochondrial oxidative phosphorylation (OXPHOS) is critical for energy (ATP) production in eukaryotic cells. It was previously shown that genes coding for mitochondrial proteins involved in energy production co-express at the RNA level. The oxidative phosphorylation system (OXPHOS) is responsible for 90% of adenosine triphosphate (ATP) production in a respiring cell. Five multi-subunit complexes, the respiratory chain complexes, and two additional electron carriers, coenzyme Q10 and cytochrome c, participate in OXPHOS to generate ATP [1]. The OXPHOS complexes consist of proteins encoded by both the nuclear (n = approximately 100 in humans) and the mitochondrial DNA (n = 13). (b) mRNA expression profiles for 1290 human and 1029 mouse mitochondrial compiled genes (rows) across 79 human (left) and 53 (right) mouse tissues (columns). Clusters enriched in genes belonging to the same functional classification are labeled between brackets

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