Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect

Am J Hum Genet. 2010 Jul 9;87(1):115-22. doi: 10.1016/j.ajhg.2010.06.004.


We investigated the genetic basis for a global and uniform decrease in mitochondrial translation in fibroblasts from patients in two unrelated pedigrees who developed Leigh syndrome, optic atrophy, and ophthalmoplegia. Analysis of the assembly of the oxidative phosphorylation complexes showed severe decreases of complexes I, IV, and V and a smaller decrease in complex III. The steady-state levels of mitochondrial mRNAs, tRNAs, and rRNAs were not reduced, nor were those of the mitochondrial translation elongation factors or the protein components of the mitochondrial ribosome. Using homozygosity mapping, we identified a 1 bp deletion in C12orf65 in one patient, and DNA sequence analysis showed a different 1 bp deletion in the second patient. Both mutations predict the same premature stop codon. C12orf65 belongs to a family of four mitochondrial class I peptide release factors, which also includes mtRF1a, mtRF1, and Ict1, all characterized by the presence of a GGQ motif at the active site. However, C12orf65 does not exhibit peptidyl-tRNA hydrolase activity in an in vitro assay with bacterial ribosomes. We suggest that it might play a role in recycling abortive peptidyl-tRNA species, released from the ribosome during the elongation phase of translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Child
  • Child, Preschool
  • Electron Transport Chain Complex Proteins / genetics
  • Electron Transport Chain Complex Proteins / metabolism
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Leigh Disease / genetics*
  • Leigh Disease / metabolism
  • Male
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Proteins
  • Mutation
  • Ophthalmoplegia / genetics*
  • Ophthalmoplegia / metabolism
  • Optic Atrophy / genetics*
  • Optic Atrophy / metabolism
  • Oxidative Phosphorylation
  • Pedigree
  • Peptide Elongation Factors / metabolism
  • Peptide Termination Factors / genetics*
  • Peptide Termination Factors / metabolism
  • Protein Biosynthesis
  • RNA, Messenger / metabolism
  • RNA, Ribosomal / metabolism
  • RNA, Transfer / metabolism
  • Ribosomes / metabolism
  • Young Adult


  • C12orf65 protein, human
  • Electron Transport Chain Complex Proteins
  • Mitochondrial Proteins
  • Peptide Elongation Factors
  • Peptide Termination Factors
  • RNA, Messenger
  • RNA, Ribosomal
  • RNA, Transfer

Associated data

  • RefSeq/NM_001545
  • RefSeq/NM_004294
  • RefSeq/NM_019041
  • RefSeq/NM_152269