The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number
Abstract
Mechanisms of mitochondrial DNA (mtDNA) maintenance have recently gained wide interest owing to their role in inherited diseases as well as in aging. Twinkle is a new mitochondrial 5'-3' DNA helicase, defects of which we have previously shown to underlie a mitochondrial disease, progressive external ophthalmoplegia with multiple mtDNA deletions. Mouse Twinkle is highly similar to the human counterpart, suggesting conserved function. Here, we have characterized the mouse Twinkle gene and expression profile and report that the expression patterns are not conserved between human and mouse, but are synchronized with the adjacent gene MrpL43, suggesting a shared promoter. To elucidate the in vivo role of Twinkle in mtDNA maintenance, we generated two transgenic mouse lines overexpressing wild-type Twinkle. We could demonstrate for the first time that increased expression of Twinkle in muscle and heart increases mtDNA copy number up to 3-fold higher than controls, more than any other factor reported to date. Additionally, we utilized cultured human cells and observed that reduced expression of Twinkle by RNA interference mediated a rapid drop in mtDNA copy number, further supporting the in vivo results. These data demonstrate that Twinkle helicase is essential for mtDNA maintenance, and that it may be a key regulator of mtDNA copy number in mammals.
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“Twinkle is essential for mtDNA maintenance and copy number (Tyynismaa et al., 2004).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Tyynismaa et al., 2004
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“Conversely, systemic Twinkle overexpression in a transgenic mouse causes a significant increase in mtDNA copy number (Tyynismaa et al., 2004)”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Tyynismaa et al., 2004
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“Mice null for the mitochondrial helicase Twinkle have impaired respiratory chain activity and muscle atrophy, but no defect in exercise capacity (285).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [285]
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Metadata
- Authors
- Tyynismaa, H., Sembongi, H., Bokori-Brown, M., Granycome, C., Ashley, N., Poulton, J., Jalanko, A., Spelbrink, J. N., Holt, I. J., & Suomalainen, A.
- Affiliations
- University of Helsinki (FI)
- MRC Mitochondrial Biology Unit (GB)
- John Radcliffe Hospital (GB)
- Institute for Molecular Medicine Finland (FI)
- Corresponding author
- Tyynismaa, Henna
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-10-27
- Volume
- 13
- Issue
- 24
- Pages
- 3219-3227
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2154067341
- Cited by
- 250
- References
- 36
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 13 · 2023: 5 · 2022: 13 · 2021: 9 · 2020: 11 · 2019: 6 · 2018: 13 · 2017: 10 · 2016: 12 · 2015: 15 · 2014: 10 · 2013: 14 · 2012: 10
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- Twinkle helicase, mitochondrial DNA maintenance, mitochondrial DNA copy number, mitochondrial disease, chronic progressive external ophthalmoplegia, mitochondrial DNA deletions, transgenic overexpression, RNA interference, muscle, heart, mouse model
- MeSH terms
- Animals, DNA Helicases, DNA, Mitochondrial, Humans, Mitochondria, Gene Dosage, DNA Primase, Gene Expression Profiling, Mitochondrial Proteins, RNA Interference, Mice
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