ArticleNucleic acids research2021
Single-molecule mitochondrial DNA sequencing shows no evidence of CpG methylation in human cells and tissues.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans.Proceedings of the National Academy of Sciences of the United States of America · 2025Trial
- Preliminary Analysis of CpG, CHG and CHH Methylation in the Mitochondrial Control Region of Dogs With Malignant Mammary Gland Tumours.Animal genetics · 2026Article
- The mitochondrial protease, LonP1, is a potential cardioprotective target for attenuating doxorubicin-induced cardiomyocyte death.Journal of translational medicine · 2026Article
- Population-scale detection of methylation outliers from long-read genome sequencing.medRxiv : the preprint server for health sciences · 2026Article
- Review
- Commentary: Novel mtDNA methylation-associated prognostic signatures in colorectal cancer.Frontiers in oncology · 2026Article
- Altered mitochondrial DNA methylation in blood in individuals with mild cognitive impairment.Epigenomics · 2025Article
- Effective Reduction in Nuclear DNA Contamination Allows Sensitive Mitochondrial DNA Methylation Determination by LC-MS/MS.International journal of molecular sciences · 2025Article
- Pyruvate kinase M2 activation reprograms mitochondria in CD8 T cells, enhancing effector functions and efficacy of anti-PD1 therapy.Cell metabolism · 2025Article
- Mitochondrial DNA and the largest nuclear-mitochondrial DNA in Arabidopsis can be separated by their methylation levels.Plant physiology · 2025Article
- MitSorter: a standalone tool for accurate discrimination of mtDNA and NuMT ONT reads based on differential methylation.Bioinformatics advances · 2025Article
- Mitochondrial DNA Mutations and Epigenetic Regulation in Type 2 Diabetes Mellitus Development.British journal of biomedical science · 2025Review
- Mitochondrial methylation is linked to sexually dimorphic growth in Nile tilapia (Frontiers in cell and developmental biology · 2025Article
- Mitochondrial epigenetic mechanisms in cancer: an updated overview.Frontiers in cell and developmental biology · 2025Review
- Critical assessment of nanopore sequencing for the detection of multiple forms of DNA modifications.bioRxiv : the preprint server for biology · 2024Article
- Optimized bisulfite sequencing analysis reveals the lack of 5-methylcytosine in mammalian mitochondrial DNA.BMC genomics · 2023Article
- Navigating the pitfalls of mapping DNA and RNA modifications.Nature reviews. Genetics · 2023Review
- Nanopore long-read next-generation sequencing for detection of mitochondrial DNA large-scale deletions.Frontiers in genetics · 2023Article
- Mitochondrial DNA methylation in metabolic associated fatty liver disease.Frontiers in nutrition · 2023Article
- Editorial: Role of genetics, epigenetics, and environmental factors in human complex diseases from the mitochondrial point of view.Frontiers in endocrinology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Methylation on CpG residues is one of the most important epigenetic modifications of nuclear DNA, regulating gene expression. Methylation of mitochondrial DNA (mtDNA) has been studied using whole genome bisulfite sequencing (WGBS), but recent evidence has uncovered technical issues which introduce a potential bias during methylation quantification. Here, we validate the technical concerns of WGBS, and develop and assess the accuracy of a new protocol for mtDNA nucleotide variant-specific methylation using single-molecule Oxford Nanopore Sequencing (ONS). Our approach circumvents confounders by enriching for full-length molecules over nuclear DNA. Variant calling analysis against showed that 99.5% of homoplasmic mtDNA variants can be reliably identified providing there is adequate sequencing depth. We show that some of the mtDNA methylation signal detected by ONS is due to sequence-specific false positives introduced by the technique. The residual signal was observed across several human primary and cancer cell lines and multiple human tissues, but was always below the error threshold modelled using negative controls. We conclude that there is no evidence for CpG methylation in human mtDNA, thus resolving previous controversies. Additionally, we developed a reliable protocol to study epigenetic modifications of mtDNA at single-molecule and single-base resolution, with potential applications beyond CpG methylation.
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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.