Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes

Mol Cell Biol. 1992 Feb;12(2):480-90. doi: 10.1128/mcb.12.2.480-490.1992.


Cytoplasts from two unrelated patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) harboring an A----G transition at nucleotide position 3243 in the tRNA(Leu(UUR)) gene of the mitochondrial genome were fused with human cells lacking endogenous mitochondrial DNA (mtDNA) (rho 0 cells). Selected cybrid lines, containing less than 15 or greater than or equal to 95% mutated genomes, were examined for differences in genetic, biochemical, and morphological characteristics. Cybrids containing greater than or equal to 95% mutant mtDNA, but not those containing normal mtDNA, exhibited decreases in the rates of synthesis and in the steady-state levels of the mitochondrial translation products. In addition, NADH dehydrogenase subunit 1 (ND 1) exhibited a slightly altered mobility on polyacrylamide gel electrophoresis. The mutation also correlated with a severe respiratory chain deficiency. A small but consistent increase in the steady-state levels of an RNA transcript corresponding to 16S rRNA + tRNA(Leu(UUR)) + ND 1 genes was detected. However, there was no evidence of major errors in processing of the heavy-strand-encoded transcripts or of altered steady-state levels or ratios of mitochondrial rRNAs or mRNAs. These results provide evidence for a direct relationship between the tRNALeu(UUR) mutation and the pathogenesis of this mitochondrial disease.

Publication types

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

MeSH terms

  • Acidosis, Lactic / genetics
  • Acidosis, Lactic / metabolism
  • Adolescent
  • Blotting, Northern
  • Brain Diseases, Metabolic / genetics*
  • Brain Diseases, Metabolic / metabolism
  • Cell Line
  • Cerebrovascular Disorders / genetics
  • Cerebrovascular Disorders / metabolism
  • Child
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Hybrid Cells
  • Immunohistochemistry
  • Mitochondria / metabolism*
  • Mutation / genetics
  • Oxygen Consumption
  • Protein Biosynthesis*
  • RNA, Transfer, Leu / genetics*
  • Syndrome


  • DNA, Mitochondrial
  • RNA, Transfer, Leu