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Mitochondrial DNA mutations in human colonic crypt stem cells
Open accessAbstract
The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.
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“several studies have related mtDNA defects to human stem cell aging100–102.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [100]
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“Clonal expansion of mtDNA mutations has been described in numerous tissues from aged individuals, such as skeletal muscle (Fayet et al., 2002; Muller-Hocker et al., 1993), substantia nigra neurons (Cottrell et al., 2001; Kraytsberg et al., 2006), heart (Muller-Hocker, 1989) and colonic crypts (Taylor et al., 2003).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Taylor et al., 2003
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Metadata
- Authors
- Taylor, R. W., Barron, M. J., Borthwick, G. M., Gospel, A., Chinnery, P. F., Samuels, D. C., Taylor, G. A., Plusa, S. M., Needham, S. J., Greaves, L. C., Kirkwood, T. B. L., & Turnbull, D. M.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Turnbull, Douglass M.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2003-11-01
- Volume
- 112
- Issue
- 9
- Pages
- 1351-1360
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC228466
- OpenAlex
- W2158615962
- Cited by
- 530
- References
- 48
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 12 · 2023: 14 · 2022: 15 · 2021: 20 · 2020: 23 · 2019: 13 · 2018: 17 · 2017: 18 · 2016: 25 · 2015: 16 · 2014: 40 · 2013: 25 · 2012: 23
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust
- Cancer Research UK
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BEP17 042)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- mitochondrial DNA mutations, mitochondrial genome, electron transport chain, uniparental inheritance, mtDNA polymorphisms, aging, cancer, mutation frequency
- MeSH terms
- Aged, Aged, 80 and over, Colon, DNA Replication, DNA, Mitochondrial, Electron Transport, Humans, Mathematics, Middle Aged, Models, Genetic, Mutation, Stem Cells
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