The mitochondrial tRNALeu(UUR) mutation in MELAS: a model for pathogenesis

Eric A. Schon, Yasutoshi Koga, Mercy Davidson, Carlos T. Moraes, Michael P. King

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

The A → G transition at nucleotide 3243 of the mitochondrial tRNALeu(UUR) gene has been associated with MELAS, a maternally-inherited mitochondrial disorder. We recently transferred mitochondria harboring this mtDNA mutation into a human cell line devoid of endogenous mtDNA (ρo cells), and showed: (1) decreased rate of synthesis and of steady-state levels of mitochondrial translational products, (2) reduced respiratory chain function and (3) increased amounts of a novel unprocessed RNA species (termed by us RNA 19) derived from transcription of the 16S rRNA + tRNALeu(UUR) + ND 1 genes. Because RNA 19 contains rRNA sequences, we propose that this molecule is incorporated into mitochondrial ribosomes, and interferes disproportionately with mitochondrial translation, thereby causing the phenotypic changes associated with MELAS.

Original languageEnglish (US)
Pages (from-to)206-209
Number of pages4
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1101
Issue number2
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • Mitochondrial disease
  • Mitochondrion
  • mtDNA
  • Ribosome
  • rRNA
  • Translation

ASJC Scopus subject areas

  • Biophysics

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