Functional consequences of mitochondrial tRNATrp and tRNA Arg mutations causing combined OXPHOS defects

Paulien Smits, Sandy Mattijssen, Eva Morava, Mariël Van Den Brand, Frans Van Den Brandt, Frits Wijburg, Ger Pruijn, Jan Smeitink, Leo Nijtmans, Richard Rodenburg, Lambert Van Den Heuvel

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Combined oxidative phosphorylation (OXPHOS) system deficiencies are a group of mitochondrial disorders that are associated with a range of clinical phenotypes and genetic defects. They occur in approximately 30% of all OXPHOS disorders and around 4% are combined complex I, III and IV deficiencies. In this study we present two mutations in the mitochondrial tRNA Trp (MT-TW) and tRNA Arg (MT-TR) genes, m.5556GA and m.10450AG, respectively, which were detected in two unrelated patients showing combined OXPHOS complex I, III and IV deficiencies and progressive multisystemic diseases. Both mitochondrial tRNA mutations were almost homoplasmic in fibroblasts and muscle tissue of the two patients and not present in controls. Patient fibroblasts showed a general mitochondrial translation defect. The mutations resulted in lowered steady-state levels and altered conformations of the tRNAs. Cybrid cell lines showed similar tRNA defects and impairment of OXPHOS complex assembly as patient fibroblasts. Our results show that these tRNA Trp and tRNA Arg mutations cause the combined OXPHOS deficiencies in the patients, adding to the still expanding group of pathogenic mitochondrial tRNA mutations.

Original languageEnglish (US)
Pages (from-to)324-329
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number3
StatePublished - Mar 2010


  • Combined OXPHOS defects
  • Mitochondrial DNA
  • Molecular mechanism
  • TRNAArg
  • TRNATrp

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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