ArticleProceedings of the National Academy of Sciences of the United States of America2023
High-frequency and functional mitochondrial DNA mutations at the single-cell level.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Mitochondria: a breakthrough in combating rheumatoid arthritis.Frontiers in medicine · 2024Pooled it
- Review
- Review
- Integrated genomic and transcriptomic approaches reveal oxidative stress adaptation mechanisms in a mesotrione-resistant Amaranthus tuberculatus biotype.Pest management science · 2026Article
- Large-scale human genomic resources drive innovations toward forensic intelligent source attribution and precision identification.International journal of legal medicine · 2026Review
- Single-cell Omics Assessment of Mitochondrial Function: Current Status and Future Perspectives.Genomics, proteomics & bioinformatics · 2026Review
- Pseudoephedrine Improves Chronic Obstructive Pulmonary Disease by Regulating Airway Senescence and Mitochondrial Function through PI3K/AKT/mTOR Axis.Biomolecules & therapeutics · 2026Article
- Mitochondrial cardiovascular diseases: molecular mechanisms, multi-omics exploration and therapeutic strategies.Journal of advanced research · 2026Review
- Single-cell mitochondrial lineage tracing: Opportunities and challenges.Quantitative biology (Beijing, China) · 2026Review
- Mitochondrial disease management through phytochemical interventions.Molecular and cellular biochemistry · 2025Review
- Biomarkers of ageing of humans and non-human primates.Nature reviews. Molecular cell biology · 2025Review
- Shaping Precision Medicine: The Journey of Sequencing Technologies Across Human Solid Tumors.Biomedicines · 2025Review
- Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.World journal of methodology · 2025Review
- Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations.Science advances · 2025Article
- Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).International journal of molecular medicine · 2025Review
- Mitochondrial dysfunction in the regulation of aging and aging-related diseases.Cell communication and signaling : CCS · 2025Review
- Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Advances and applications in single-cell and spatial genomics.Science China. Life sciences · 2025Review
- Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis.Nature neuroscience · 2025Article
- Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells.Genome biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Decline in mitochondrial function underlies aging and age-related diseases, but the role of mitochondrial DNA (mtDNA) mutations in these processes remains elusive. To investigate patterns of mtDNA mutations, it is particularly important to quantify mtDNA mutations and their associated pathogenic effects at the single-cell level. However, existing single-cell mtDNA sequencing approaches remain inefficient due to high cost and low mtDNA on-target rates. In this study, we developed a cost-effective mtDNA targeted-sequencing protocol called single-cell sequencing by targeted amplification of multiplex probes (scSTAMP) and experimentally validated its reliability. We then applied our method to assess single-cell mtDNA mutations in 768 B lymphocytes and 768 monocytes from a 76-y-old female. Across 632 B lymphocyte and 617 monocytes with medium mtDNA coverage over >100×, our results indicated that over 50% of cells carried at least one mtDNA mutation with variant allele frequencies (VAFs) over 20%, and that cells carried an average of 0.658 and 0.712 such mutation for B lymphocytes and monocytes, respectively. Surprisingly, more than 20% of the observed mutations had VAFs of over 90% in either cell population. In addition, over 60% of the mutations were in protein-coding genes, of which over 70% were nonsynonymous, and more than 50% of the nonsynonymous mutations were predicted to be highly pathogenic. Interestingly, about 80% of the observed mutations were singletons in the respective cell populations. Our results revealed mtDNA mutations with functional significance might be prevalent at advanced age, calling further investigation on age-related mtDNA mutation dynamics at the single-cell level.
Indexed as
Identifiers
What OpenQuestion holds
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.