ArticleEpigenetics & chromatin2018
Modulation of mitochondrial DNA copy number in a model of glioblastoma induces changes to DNA methylation and gene expression of the nuclear genome in tumours.
Article in Epigenetics & chromatin, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Epigenome-wide association study of mitochondrial genome copy number.Human molecular genetics · 2021Pooled it
- Mitochondrial DNA Content Modulates Chemosensitivity and Cellular Adaptation in Glioblastoma Cells.The Eurasian journal of medicine · 2026Article
- Mitochondrial DNA copy number reduction viaEpigenomics · 2026Article
- The nuclear and mitochondrial genomes need to tango. How is their dance synchronized during development?NAR molecular medicine · 2026Article
- Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review).Molecular medicine reports · 2025Review
- MtDNA copy number enrichment is associated with poor prognosis and eosinophilic morphology in clear cell renal cell carcinoma.Pathology oncology research : POR · 2025Article
- The role of mtDNA in oocyte quality and embryo development.Molecular reproduction and development · 2023Review
- Does supplementation of oocytes with additional mtDNA influence developmental outcome?iScience · 2023Article
- Mitoepigenetics and gliomas: epigenetic alterations to mitochondrial DNA and nuclear DNA alter mtDNA expression and contribute to glioma pathogenicity.Frontiers in neurology · 2023Review
- Insights regarding mitochondrial DNA copy number alterations in human cancer (Review).International journal of molecular medicine · 2022Review
- Mitochondrial supplementation of Sus scrofa metaphase II oocytes alters DNA methylation and gene expression profiles of blastocysts.Epigenetics & chromatin · 2022Article
- Mitochondrial genomic integrity and the nuclear epigenome in health and disease.Frontiers in endocrinology · 2022Article
- Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity.Oxidative medicine and cellular longevity · 2022Article
- Mitochondrial DNA Alterations in Glioblastoma (GBM).International journal of molecular sciences · 2021Review
- Low biological fluctuation of mitochondrial CpG and non-CpG methylation at the single-molecule level.Scientific reports · 2021Article
- Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease.Genome research · 2021Article
- Structure, mechanism, and regulation of mitochondrial DNA transcription initiation.The Journal of biological chemistry · 2020Review
- Review
- Association between sperm mitochondarial DNA copy number and nuclear DNA methylation.Epigenomics · 2020Article
- Mitochondrial DNA copy number can influence mortality and cardiovascular disease via methylation of nuclear DNA CpGs.Genome medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere are multiple copies of mitochondrial DNA (mtDNA) present in each cell type, and they are strictly regulated in a cell-specific manner by a group of nuclear-encoded mtDNA-specific replication factors. This strict regulation of mtDNA copy number is mediated by cell-specific DNA methylation of these replication factors. Glioblastoma multiforme, HSR-GBM1, cells are hyper-methylated and maintain low mtDNA copy number to support their tumorigenic status. We have previously shown that when HSR-GBM1 cells with 50% of their original mtDNA content were inoculated into mice, tumours grew more aggressively than non-depleted cells. However, when the cells possessed only 3% and 0.2% of their original mtDNA content, tumour formation was less frequent and the initiation of tumorigenesis was significantly delayed. Importantly, the process of tumorigenesis was dependent on mtDNA copy number being restored to pre-depletion levels.
resultsBy performing whole genome MeDIP-Seq and RNA-Seq on tumours generated from cells possessing 100%, 50%, 0.3% and 0.2% of their original mtDNA content, we determined that restoration of mtDNA copy number caused significant changes to both the nuclear methylome and its transcriptome for each tumour type. The affected genes were specifically associated with gene networks and pathways involving behaviour, nervous system development, cell differentiation and regulation of transcription and cellular processes. The mtDNA-specific replication factors were also modulated.
conclusionsOur results highlight the bidirectional control of the nuclear and mitochondrial genomes through modulation of DNA methylation to control mtDNA copy number, which, in turn, modulates nuclear gene expression during tumorigenesis.
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Registered trials
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