Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 401, Issue 1, Pages 26-31Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.08.143
Keywords
Mitochondrial diseases; Mitochondrial DNA; Tfam; Mito-mouse
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Funding
- Takeda Science Foundation
- Japan Society for Promotion of Science (JSPS)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Ministry of Health, Labor and Welfare [20B-13]
- Grants-in-Aid for Scientific Research [22650091, 21240044] Funding Source: KAKEN
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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. (C) 2010 Elsevier Inc. All rights reserved.
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