MtDNA mutation in MERRF syndrome causes defective aminoacylation of tRNA(Lys) and premature translation termination

Nat Genet. 1995 May;10(1):47-55. doi: 10.1038/ng0595-47.


We have investigated the pathogenetic mechanism of the mitochondrial tRNA(Lys) gene mutation (position 8344) associated with MERRF encephalomyopathy in several mitochondrial DNA (mtDNA)-less cell transformants carrying the mutation and in control cells. A decrease of 50-60% in the specific tRNA(Lys) aminoacylation capacity per cell was found in mutant cells. Furthermore, several lines of evidence reveal that the severe protein synthesis impairment in MERRF mutation-carrying cells is due to premature termination of translation at each or near each lysine codon, with the deficiency of aminoacylated tRNA(Lys) being the most likely cause of this phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • DNA, Mitochondrial*
  • Humans
  • Lysine / metabolism
  • MERRF Syndrome / genetics*
  • Methionine / metabolism
  • Mitochondria / metabolism
  • Mutation*
  • NADH Dehydrogenase / biosynthesis
  • Oxygen Consumption
  • Peptide Chain Termination, Translational*
  • Protein Biosynthesis
  • RNA, Transfer, Amino Acyl / genetics
  • RNA, Transfer, Amino Acyl / metabolism
  • RNA, Transfer, Lys* / chemistry
  • RNA, Transfer, Lys* / metabolism*
  • Ribosomes / metabolism
  • Transformation, Genetic


  • DNA, Mitochondrial
  • RNA, Transfer, Amino Acyl
  • RNA, Transfer, Lys
  • Methionine
  • NADH Dehydrogenase
  • Lysine