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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734
Self-citationMitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice
Larsson, N.-G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G. S., & Clayton, D. A. (1998) · Nature Genetics · doi:10.1038/ng0398-231 · Cited by 1,594
Mitochondrial transcription factor A regulates mtDNA copy number in mammals
Ekstrand, M. I. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh109 · Cited by 919
Thymidine Phosphorylase Gene Mutations in MNGIE, a Human Mitochondrial Disorder
Nishino, I., Spinazzola, A., & Hirano, M. (1999) · Science · doi:10.1126/science.283.5402.689 · Cited by 899
Spelbrink, J. N., Li, F.-Y., Tiranti, V., Nikali, K., Yuan, Q.-P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L., et al. (2001) · Nature Genetics · doi:10.1038/90058 · Cited by 882
Van Goethem, G., Dermaut, B., Löfgren, A., Martin, J.-J., & Van Broeckhoven, C. (2001) · Nature Genetics · doi:10.1038/90034 · Cited by 841
Gunning, P. W., Leavitt, J. C., Muscat, G. E. O., Ng, S. Y., & Kedes, L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.14.4831 · Cited by 739
Role of Adenine Nucleotide Translocator 1 in mtDNA Maintenance
Kaukonen, J., Juselius, J. K., Tiranti, V., Kyttälä, A., Zeviani, M., Comi, G. P., Keränen, S., Peltonen, L., & Suomalainen, A. (2000) · Science · doi:10.1126/science.289.5480.782 · Cited by 641
Luoma, P., Melberg, A., Rinne, J. O., Kaukonen, J. A., Nupponen, N. N., Chalmers, R. M., Oldfors, A., Rautakorpi, I., Peltonen, L., Majamaa, K., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16983-3 · Cited by 548
Reconstitution of a minimal mtDNA replisome in vitro
Korhonen, J. A., Pham, X. H., Pellegrini, M., & Falkenberg, M. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600257 · Cited by 404
Composition and dynamics of human mitochondrial nucleoids.
Garrido, N., Griparić, L., Jokitalo, E., Wartiovaara, J., van der Bliek, A. M., & Spelbrink, J. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-07-0399 · Cited by 390
Organization and dynamics of human mitochondrial DNA
Legros, F., Malka, F., Frachon, P., Lombès, A., & Rojo, M. (2004) · Journal of Cell Science · doi:10.1242/jcs.01134 · Cited by 383
Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice
Cerritelli, S. M., Frolova, E. G., Feng, C., Grinberg, A., Love, P. E., & Crouch, R. J. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00088-1 · Cited by 358
The functional organization of mitochondrial genomes in human cells
Iborra, F. J., Kimurâ, H., & Cook, P. R. (2004) · BMC Biology · doi:10.1186/1741-7007-2-9 · Cited by 339
Korhonen, J. A., Gaspari, M., & Falkenberg, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306981200 · Cited by 298
The Large Subunit of the Mammalian Mitochondrial Ribosome
Koc, E. C., Burkhart, W., Blackburn, K., Moyer, M. B., Schlatzer, D., Moseley, M. A., & Spremulli, L. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106510200 · Cited by 252
The Small Subunit of the Mammalian Mitochondrial Ribosome
Koc, E. C., Burkhart, W., Blackburn, K., Moseley, M. A., & Spremulli, L. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100727200 · Cited by 246
Suomalainen, A., Majander, A. S., Haltia, M., Somer, H., Lönnqvist, J. K., Savontaus, M. L., & Peltonen, L. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115856 · Cited by 242
Mammalian Mitochondrial DNA Replicates Bidirectionally from an Initiation Zone
Bowmaker, M., Yang, M., Yasukawa, T., Reyes, A., Jacobs, H. T., Huberman, J. A., & Holt, I. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308028200 · Cited by 218
Spelbrink, J. N., Toivonen, J. M., Hakkaart, G. A. J., Kurkela, J. M., Cooper, H. M., Lehtinen, S. K., Lecrenier, N., Back, J. W., Speijer, D., Foury, F., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000559200 · Cited by 193
Mutations of ANT1 , Twinkle , and POLG1 in sporadic progressive external ophthalmoplegia (PEO)
Agostino, A., Valletta, L., Chinnery, P. F., Ferrari, G., Carrara, F., Taylor, R. W., Schaefer, A. M., Turnbull, D. M., Tiranti, V., & Zeviani, M. (2003) · Neurology · doi:10.1212/01.wnl.0000056088.09408.3c · Cited by 153
Autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA
Suomalainen, A., Majander, A. S., Wallin, M., Setälä, K., KONTULA, K. K., Leinonen, H., Salmi, T. T., Paetau, A. E., Haltia, M., Valanne, L. K., et al. (1997) · Neurology · doi:10.1212/wnl.48.5.1244 · Cited by 140
Suzuki, T., Terasaki, M., Takemoto‐Hori, C., Hanada, T., Ueda, T., Wada, A., & Watanabe, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100432200 · Cited by 115
Diseases caused by nuclear genes affecting mtDNA stability
Suomalainen, A., & Kaukonen, J. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1379 · Cited by 109
Matsushima, Y., Garesse, R., & Kaguni, L. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401643200 · Cited by 86
Mitochondrial Nucleoid and Transcription Factor A
Kanki, T., Nakayama, H., Sasaki, N., Takio, K., Alam, T. I., Hamasaki, N., & Kang, D. (2004) · Springer eBooks · doi:10.1007/978-3-662-41088-2_7 · Cited by 73
Mitochondrial nucleoid and transcription factor A
KANKI, T., NAKAYAMA, H., SASAKI, N., TAKIO, K., ALAM, T. I., HAMASAKI, N., & KANG, D. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1293.007 · Cited by 70
Gensler, S. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.17.3657 · Cited by 69
Meyer, R. G., Meyer‐Ficca, M. L., Jacobson, E. L., & Jacobson, M. K. (2003) · Gene · doi:10.1016/s0378-1119(03)00738-8 · Cited by 66
Matsushima, Y., Matsumura, K., Ishii, S., Inagaki, H., Suzuki, T., Matsuda, Y., Beck, K., & Kitagawa, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303842200 · Cited by 62
A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia
Deschauer, M., Kiefer, R., Blakely, E. L., He, L., Zierz, S., Turnbull, D. M., & Taylor, R. W. (2003) · Neuromuscular Disorders · doi:10.1016/s0960-8966(03)00071-3 · Cited by 54
Clinical and molecular features of adPEO due to mutations in the Twinkle gene
Lewis, S., Hutchison, W. M., Thyagarajan, D. E., & Dahl, H. M. (2002) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(02)00190-9 · Cited by 48
Lefai, É., Calleja, M., de Mena, I. R., Lagina, A. T., Kaguni, L. S., & Garesse, R. (2000) · Molecular and General Genetics MGG · doi:10.1007/s004380000301 · Cited by 34
Quantitative Analysis of Human DNA Sequences by PCR and Solid-Phase Minisequencing
Suomalainen, A., & Syvänen, A. (2000) · Molecular Biotechnology · doi:10.1385/mb:15:2:123 · Cited by 34
Zhang, L., Ding, J.-H., Yang, B.-Z., He, G.-C., & Roe, C. R. (2003) · Genomics · doi:10.1016/s0888-7543(03)00211-8 · Cited by 20
Quantitative Analysis of RNA Species by PCR and Solid-Phase Minisequencing
Suomalainen, A., & Syvänen, A. (1998) · Humana Press eBooks · doi:10.1385/0-89603-494-1:121 · Cited by 7
Cited by
Sorted by citations
Transcriptional paradigms in mammalian mitochondrial biogenesis and function
Scarpulla, R. C. (2008) · Physiological Reviews · doi:10.1152/physrev.00025.2007 · Cited by 1,666
Maintenance and Expression of Mammalian Mitochondrial DNA
Gustafsson, C. M., Falkenberg, M., & Larsson, N. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014402 · Cited by 688
ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells
Lewis, S. C., Uchiyama, L. F., & Nunnari, J. (2016) · Science · doi:10.1126/science.aaf5549 · Cited by 673
Schapira, A. H. V. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68970-8 · Cited by 617
The role of mitochondria in the pathogenesis of type 2 diabetes
Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
