The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria
Abstract
The gene products involved in mammalian mitochondrial DNA (mtDNA) maintenance and organization remain largely unknown. We report here a novel mitochondrial protein, Twinkle, with structural similarity to phage T7 gene 4 primase/helicase and other hexameric ring helicases. Twinkle colocalizes with mtDNA in mitochondrial nucleoids. Screening of the gene encoding Twinkle in individuals with autosomal dominant progressive external ophthalmoplegia (adPEO), associated with multiple mtDNA deletions, identified 11 different coding-region mutations co-segregating with the disorder in 12 adPEO pedigrees of various ethnic origins. The mutations cluster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle is inferred to be critical for lifetime maintenance of human mtDNA integrity.
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In the citing paper
“It is involved in D-loop formation and localizes to the nucleoid (Jemt et al., 2015; Milenkovic et al., 2013; Spelbrink et al., 2001).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Spelbrink et al., 2001
In the citing paper
“It was classified as a helicase based on sequence similarity to bacteriophage T7 gene 4 primase-helicase (T7 gp4) (Spelbrink et al., 2001).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Spelbrink et al., 2001
In the citing paper
“In all, 31 dominant and 3 recessive mutations have been recognized, the majority of which cause age-related disease (Sanchez-Martinez et al., 2012; Spelbrink et al., 2001).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Spelbrink et al., 2001
Citations
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Mitochondrial DNA mutations in human disease
Taylor, R. W., & Turnbull, D. M. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1606 · Cited by 1,922
Mitochondrial form and function
Friedman, J. R., & Nunnari, J. (2014) · Nature · doi:10.1038/nature12985 · Cited by 1,803
Mitochondrial Respiratory-Chain Diseases
DiMauro, S., & Schon, E. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmra022567 · Cited by 1,672
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Metadata
- Authors
- Spelbrink, J. N., Li, F.-Y., Tiranti, V., Nikali, K., Yuan, Q.-P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L., Santoro, L., Toscano, A., Fabrizi, G.-M., Somer, H., Croxen, R., Beeson, D., Poulton, J., Suomalainen, A., Jacobs, H. T., Zeviani, M., & Larsson, C.
- Affiliations
- Tampere University Hospital (FI)
- Karolinska University Hospital (SE)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Pakistan Institute of Medical Sciences (PK)
- University of Milan (IT)
- University of Naples Federico II (IT)
- University of Verona (IT)
- University of Helsinki (FI)
- John Radcliffe Hospital (GB)
- Montreal Neurological Institute and Hospital (CA)
- Corresponding author
- Spelbrink, Johannes N.
- ORCID
- Venue
- Nature Genetics
- Published
- 2001-07
- Volume
- 28
- Issue
- 3
- Pages
- 223-231
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1551996591
- Cited by
- 882
- References
- 48
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 25 · 2023: 22 · 2022: 28 · 2021: 19 · 2020: 35 · 2019: 29 · 2018: 21 · 2017: 25 · 2016: 40 · 2015: 36 · 2014: 43 · 2013: 48 · 2012: 42
- FWCI
- 16.33
- Type
- journal article
- Language
- en
- Update notices
- correction (2001-09-01)
- Open access
- closed
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (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 › Genetics › Genomics and Rare Diseases
- Keywords
- mitochondrial DNA deletions, chronic progressive external ophthalmoplegia, mtDNA maintenance, mitochondrial nucleoids, protein mutations, co-segregation, mitochondrial DNA integrity
- MeSH terms
- Amino Acid Sequence, Cell Compartmentation, Chromosomes, Human, Pair 10, DNA Helicases, DNA, Mitochondrial, Female, Finland, Heterozygote, Humans, Italy, Genetic Linkage, Male, Molecular Sequence Data, Mutation, Pakistan, Pedigree, Protein Conformation, Ophthalmoplegia, Chronic Progressive External, Sequence Deletion, Sequence Homology, Amino Acid, DNA Primase, Protein Transport, Mitochondrial Proteins
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