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Mitochondrial dysfunction leads to telomere attrition and genomic instability
Open accessAbstract
Summary: Mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence, apoptosis, aging and aging‐associated pathologies. Telomere shortening and genomic instability have also been associated with replicative senescence, aging and cancer. Here we show that mitochondrial dysfunction leads to telomere attrition, telomere loss, and chromosome fusion and breakage, accompanied by apoptosis. An antioxidant prevented telomere loss and genomic instability in cells with dysfunctional mitochondria, suggesting that reactive oxygen species are mediators linking mitochondrial dysfunction and genomic instability. Further, nuclear transfer protected genomes from telomere dysfunction and promoted cell survival by reconstitution with functional mitochondria. This work links mitochondrial dysfunction and genomic instability and may provide new therapeutic strategies to combat certain mitochondrial and aging‐associated pathologies.
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“FCCP treatment, which causes severe mitochondrial depolarization and thus mitochondrial dysfunction, increases ROS generation and leads to telomere attrition, telomere loss and chromosome fusions in mouse embryos (Liu et al., 2002).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Liu et al., 2002
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Metadata
- Authors
- Liu, L., Trimarchi, J. R., Smith, P. J. S., & Keefe, D. L.
- Affiliations
- Marine Biological Laboratory (US)
- Corresponding author
- Keefe, David L.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2002-09-15
- Volume
- 1
- Issue
- 1
- Pages
- 40-46
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2171912874
- Cited by
- 237
- References
- 49
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 9 · 2023: 15 · 2022: 15 · 2021: 14 · 2020: 14 · 2019: 12 · 2018: 13 · 2017: 6 · 2016: 8 · 2015: 12 · 2014: 10 · 2013: 12 · 2012: 13
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- mitochondrial dysfunction, telomere shortening, telomere loss, genomic instability, chromosome fusion, chromosome breakage, apoptosis, oxidative stress, reactive oxygen species, replicative senescence, nuclear transfer, antioxidant defense, aging
- MeSH terms
- Animals, Antioxidants, Cell Division, Cell Nucleus, Female, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mitochondria, Zygote, Tissue Transplantation, Telomere, Cellular Senescence, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Chromosome Breakage, Mice, Nuclear Transfer Techniques
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