ArticleNucleic acids research2015
Stable heteroplasmy at the single-cell level is facilitated by intercellular exchange of mtDNA.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Review
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
- Fusion Between Control Mesoangioblasts and mtDNA-Mutant Myotubes Preserves Myotube Morphology and Mitochondrial Network Organization.International journal of molecular sciences · 2026Article
- Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations.Science advances · 2025Article
- The movement of mitochondria in breast cancer: internal motility and intercellular transfer of mitochondria.Clinical & experimental metastasis · 2024Review
- Single-cell mitochondrial sequencing reveals low-frequency mitochondrial mutations in naturally aging mice.Aging cell · 2024Article
- Evolution and maintenance of mtDNA gene content across eukaryotes.The Biochemical journal · 2024Review
- Adenosine diphosphate released from stressed cells triggers mitochondrial transfer to achieve tissue homeostasis.PLoS biology · 2024Article
- Review
- Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker.Frontiers in oncology · 2024Review
- The prenatal environment and its influence on maternal and child mitochondrial DNA copy number and methylation: A review of the literature.Environmental research · 2023Review
- Highly-multiplexed and efficient long-amplicon PacBio and Nanopore sequencing of hundreds of full mitochondrial genomes.BMC genomics · 2023Article
- The Potential Use of Mitochondrial Extracellular Vesicles as Biomarkers or Therapeutical Tools.International journal of molecular sciences · 2023Review
- Highly-purified rapidly expanding clones, RECs, are superior for functional-mitochondrial transfer.Stem cell research & therapy · 2023Article
- Mitochondria on the move: Horizontal mitochondrial transfer in disease and health.The Journal of cell biology · 2023Article
- Nanopore long-read next-generation sequencing for detection of mitochondrial DNA large-scale deletions.Frontiers in genetics · 2023Article
- Association between diesel exhaust exposure and mitochondrial DNA methylation.Carcinogenesis · 2022Article
- Respiratory Complex I dysfunction in cancer: from a maze of cellular adaptive responses to potential therapeutic strategies.The FEBS journal · 2022Review
- Translocation of mitochondrial DNA into the nuclear genome blurs phylogeographic and conservation genetic studies in seabirds.Royal Society open science · 2022Article
- Identification of Somatic Mitochondrial DNA Mutations, Heteroplasmy, and Increased Levels of Catenanes in Tumor Specimens Obtained from Three Endometrial Cancer Patients.Life (Basel, Switzerland) · 2022Article
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Authors and funding
10 authors.
Funding
Abstract
Eukaryotic cells carry two genomes, nuclear (nDNA) and mitochondrial (mtDNA), which are ostensibly decoupled in their replication, segregation and inheritance. It is increasingly appreciated that heteroplasmy, the occurrence of multiple mtDNA haplotypes in a cell, plays an important biological role, but its features are not well understood. Accurately determining the diversity of mtDNA has been difficult, due to the relatively small amount of mtDNA in each cell (<1% of the total DNA), the intercellular variability of mtDNA content and mtDNA pseudogenes (Numts) in nDNA. To understand the nature of heteroplasmy, we developed Mseek, a novel technique to purify and sequence mtDNA. Mseek yields high purity (>90%) mtDNA and its ability to detect rare variants is limited only by sequencing depth, providing unprecedented sensitivity and specificity. Using Mseek, we confirmed the ubiquity of heteroplasmy by analyzing mtDNA from a diverse set of cell lines and human samples. Applying Mseek to colonies derived from single cells, we find heteroplasmy is stably maintained in individual daughter cells over multiple cell divisions. We hypothesized that the stability of heteroplasmy could be facilitated by intercellular exchange of mtDNA. We explicitly demonstrate this exchange by co-culturing cell lines with distinct mtDNA haplotypes. Our results shed new light on the maintenance of heteroplasmy and provide a novel platform to investigate features of heteroplasmy in normal and diseased states.
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