Repopulation of ?0 cells with mitochondria from a patient with a mitochondrial DNA point mutation in tRNAGly results in respiratory chain dysfunction Journal Articles uri icon

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  • Familial hypertrophic ventricular cardiomyopathy has been demonstrated to be associated with a number of mitochondrial DNA (mtDNA) mutations. A fibroblast cell line carrying a mutation in its mtDNA at position 9997 in the gene encoding tRNA glycine was obtained from a patient with hypertrophic cardiomyopathy. To demonstrate that the etiology of this disease was a result of the mtDNA mutation, cybrid clones were constructed by fusion of enucleated patient skin fibroblasts to rho0 osteosarcoma cells. Clones carrying high levels of mutant mtDNA showed predominantly cytochrome c oxidase and complex I deficiency, as well as an elevated lactate/pyruvate (L/P) ratio, a biochemical marker characteristic of respiratory chain deficiencies. Pulse-labeling experiments demonstrated a strong negative correlation between the levels of newly synthesized mtDNA-encoded polypeptides and glycine content. These data suggest that the T9997C mutation in mtDNA is causative of respiratory chain dysfunction when present at high levels of heteroplasmy.


  • Raha, Sandeep
  • Merante, Frank
  • Shoubridge, Eric
  • Myint, A Tomoko
  • Tein, Ingrid
  • Benson, Lee
  • Johns, Tim
  • Robinson, Brian H

publication date

  • 1999

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