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Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system

Overview of attention for article published in BMC Genomics, September 2015
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Title
Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system
Published in
BMC Genomics, September 2015
DOI 10.1186/s12864-015-1883-8
Pubmed ID
Authors

Robin van der Lee, Radek Szklarczyk, Jan Smeitink, Hubert J M Smeets, Martijn A. Huynen, Rutger Vogel

Abstract

Transcriptional control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study we performed RNA sequencing of two control and two complex I-deficient patient cell lines cultured in the presence of compounds that perturb mitochondrial metabolism: chloramphenicol, AICAR, or resveratrol. We combined this with a comprehensive analysis of mitochondrial and nuclear gene expression patterns, co-expression calculations and transcription factor binding sites. Our analyses show that subsets of mitochondrial OXPHOS genes respond opposingly to chloramphenicol and AICAR, whereas the response of nuclear OXPHOS genes is less consistent between cell lines and treatments. Across all samples nuclear OXPHOS genes have a significantly higher co-expression with each other than with other genes, including those encoding mitochondrial proteins. We found no evidence for complex-specific mRNA expression regulation: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of nuclear genes for OXPHOS subunits versus assembly factors, suggesting divergent transcription programs. Furthermore, complex I co-expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of novel candidates (ELK1, KLF7, SP4, EHF, ZNF143, and TEL2). OXPHOS genes share an expression program distinct from other genes encoding mitochondrial proteins, indicative of targeted nuclear regulation of a mitochondrial sub-process. Within the subset of OXPHOS genes we established a difference in expression between mitochondrial and nuclear genes, and between nuclear genes encoding subunits and assembly factors. Most transcription regulators of genes that co-express with complex I are well-established factors for OXPHOS biogenesis. For the remaining six factors we here suggest for the first time a link with transcription regulation in OXPHOS deficiency.

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Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 32%
Student > Bachelor 5 13%
Student > Master 4 11%
Professor 3 8%
Student > Doctoral Student 2 5%
Other 6 16%
Unknown 6 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 37%
Agricultural and Biological Sciences 9 24%
Medicine and Dentistry 3 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Sports and Recreations 1 3%
Other 1 3%
Unknown 9 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 September 2015.
All research outputs
#9,880,987
of 12,378,687 outputs
Outputs from BMC Genomics
#5,640
of 7,251 outputs
Outputs of similar age
#170,462
of 249,055 outputs
Outputs of similar age from BMC Genomics
#274
of 313 outputs
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