Over-expression of Tfam improves the mitochondrial disease phenotypes in a mouse model system
Open accessAbstract
The phenotypes of mitochondrial diseases caused by mutations in mitochondrial DNA (mtDNA) have been proposed to be strictly regulated by the proportion of wild-type and pathogenically mutated mtDNAs. More specifically, it is thought that the onset of the disease phenotype occurs when cells cannot maintain the proper mitochondrial function because of an over-abundance of pathological mtDNA. Therapies that cause a decrease in the pathogenic mtDNA population have been proposed as a treatment for mitochondrial diseases, but these therapies are difficult to apply in practice. In this report, we present a novel concept: to improve mitochondrial disease phenotypes via an increase in the absolute copy number of the wild-type mtDNA population in pathogenic cells even when the relative proportion of mtDNA genotypes remains unchanged. We have succeeded in ameliorating the typical symptoms of mitochondrial disease in a model mouse line by the over-expression of the mitochondrial transcription factor A (Tfam) followed by an increase of the mtDNA copy number. This new concept should lead to the development of a novel therapeutic treatment for mitochondrial diseases.
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Crossing mice overexpressing TFAM with mito-mice leads to an overall increase in mtDNA content and copy number without a decrease in the amount of deleted mtDNA.
“Another mouse model system crossed mice overexpressing TFAM with the mito-mice that have mutant mtDNA carrying a deletion of 4696 bp leading to an overall increase in mtDNA content and copy number without a decrease in the amount of deleted mtDNA (Nishiyama et al., 2010).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Nishiyama et al., 2010
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References 33 · Cited by 46
- Authors
- Nishiyama, S., Shitara, H., Nakada, K., Ono, T., Sato, A., Suzuki, H., Ogawa, T., Masaki, H., Hayashi, J.-I., & Yonekawa, H.
- Affiliations
- University of Tsukuba (JP)
- Tokyo Metropolitan Institute of Medical Science (JP)
- The University of Tokyo (JP)
- Corresponding author
- Hayashi, Jun-Ichi
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 401
- Issue
- 1
- Pages
- 26-31
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2019671050
- Cited by
- 46
- References
- 33
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 2 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2014: 2 · 2013: 1 · 2012: 6
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (acceptedVersion)
- Terrestrial Environment Research Center (University of Tsukuba) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology (20B-13)
- Takeda Science Foundation
- Ministry of Health, Labour and Welfare
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- mitochondrial disease, TFAM, mitochondrial DNA copy number, mitochondrial DNA mutations, mitochondrial dysfunction, mouse model, treatment options
- MeSH terms
- Animals, Electron Transport Complex IV, Disease Models, Animal, DNA-Binding Proteins, DNA, Mitochondrial, Male, Mice, Transgenic, Transcription Factors, Genetic Therapy, Gene Expression, Gene Dosage, Mitochondrial Proteins, Mitochondrial Diseases, Mice
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