ArticleGenome research2015
Global variability in gene expression and alternative splicing is modulated by mitochondrial content.
Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 129 citations in OpenAlex.
- Metabolic and developmental rate divergence between serially homologous cells underlies an evolutionary innovation in Drosophila.PLoS biology · 2026Article
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- Dysregulation of alternative splicing patterns in the ovaries of reproductively aged mice.Reproduction (Cambridge, England) · 2026Article
- Morphological innovation without gene co-option: thebioRxiv : the preprint server for biology · 2026Article
- Mitochondrial DNA copy number reduction viaEpigenomics · 2026Article
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- Exploring gene expression heterogeneity in burn wounds through machine learning models:Annals of medicine and surgery (2012) · 2025Article
- Mitochondrial function regulates cell growth kinetics to maintain mitochondrial homeostasis.Current biology : CB · 2025Article
- ADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation.Molecular psychiatry · 2025Article
- Gradient matching accelerates mixed-effects inference for biochemical networks.Bioinformatics (Oxford, England) · 2025Article
- Metabolic activities are selective modulators for individual segmentation clock processes.Nature communications · 2025Article
- Implications of mtDNA in human health and diseases.Biotechnologia · 2025Review
- Ginsenoside Rb2 inhibits p300-mediated SF3A2 acetylation at lysine 10 to promote Fscn1 alternative splicing against myocardial ischemic/reperfusion injury.Journal of advanced research · 2024Article
- Mitochondria: a new intervention target for tumor invasion and metastasis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Metabolic mechanisms of species-specific developmental tempo.Developmental cell · 2024Review
- Significance of quantitative analyses of the impact of heterogeneity in mitochondrial content and shape on cell differentiation.Open biology · 2024Review
- Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity.International journal of molecular sciences · 2023Review
- Article
- Position-dependent effects of RNA-binding proteins in the context of co-transcriptional splicing.NPJ systems biology and applications · 2023Article
- Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
Abstract
Noise in gene expression is a main determinant of phenotypic variability. Increasing experimental evidence suggests that genome-wide cellular constraints largely contribute to the heterogeneity observed in gene products. It is still unclear, however, which global factors affect gene expression noise and to what extent. Since eukaryotic gene expression is an energy demanding process, differences in the energy budget of each cell could determine gene expression differences. Here, we quantify the contribution of mitochondrial variability (a natural source of ATP variation) to global variability in gene expression. We find that changes in mitochondrial content can account for ∼50% of the variability observed in protein levels. This is the combined result of the effect of mitochondria dosage on transcription and translation apparatus content and activities. Moreover, we find that mitochondrial levels have a large impact on alternative splicing, thus modulating both the abundance and type of mRNAs. A simple mathematical model in which mitochondrial content simultaneously affects transcription rate and splicing site choice can explain the alternative splicing data. The results of this study show that mitochondrial content (and/or probably function) influences mRNA abundance, translation, and alternative splicing, which ultimately affects cellular phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.