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Abstract

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.

Journal

  • Biochemical and biophysical research communications

    Biochemical and biophysical research communications 401(1), 26-31, 2010-10-08

    Elsevier Inc.

Keywords

Codes

  • NII Article ID (NAID)
    120002647772
  • NII NACSIS-CAT ID (NCID)
    AA00564395
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0006-291X
  • Data Source
    IR 
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