Molecular and functional effects of the T14709C point mutation in the mitochondrial DNA of a patient with maternally inherited diabetes and deafness

Biochim Biophys Acta. 2002 Dec 12;1588(3):210-6. doi: 10.1016/s0925-4439(02)00167-9.


A heteroplasmic T to C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNA(Glu)) gene has previously been associated with maternally inherited diabetes and deafness (MIDD). To investigate the pathogenic mechanism of the T14709C mutation, we have constructed transmitochondrial cell lines by transferring fibroblasts mitochondria from a patient with the mutation into human cells lacking mitochondrial DNA (mtDNA) (rho degrees cells). Clonal cybrid cell lines were obtained containing various levels of the heteroplasmic mutation, or exclusively mutated or wild-type mtDNA. Measurement of respiratory chain enzymatic activities failed to detect a difference between the homoplasmic mutant and homoplasmic wild-type cybrid cell lines. However, a subtle decrease in the steady-state levels of tRNA(Glu) transcripts in some mutant clones. Our studies suggest that the T14709C mutation is insufficient to lead impairment of mitochondrial function in homoplasmic osteosarcoma cybrid clones, and that we cannot exclude that the T14709C mutation affects mitochondrial function by a yet unidentified mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Northern
  • Cell Fusion
  • Clone Cells
  • DNA, Mitochondrial / genetics*
  • Deafness / complications
  • Deafness / genetics*
  • Diabetes Complications
  • Diabetes Mellitus / genetics*
  • Electron Transport Complex I
  • Electron Transport Complex II
  • Electron Transport Complex III / metabolism
  • Fibroblasts / metabolism
  • Genotype
  • Humans
  • Multienzyme Complexes / metabolism
  • NADH, NADPH Oxidoreductases / metabolism
  • Oxidoreductases / metabolism
  • Point Mutation
  • RNA, Transfer, Glu / analysis
  • Succinate Dehydrogenase / metabolism


  • DNA, Mitochondrial
  • Multienzyme Complexes
  • RNA, Transfer, Glu
  • Oxidoreductases
  • Electron Transport Complex II
  • Succinate Dehydrogenase
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex I
  • Electron Transport Complex III