Mitochondrial aminoacyl-tRNA synthetases in human disease

Mol Genet Metab. 2013 Apr;108(4):206-11. doi: 10.1016/j.ymgme.2013.01.010. Epub 2013 Jan 26.


Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential in the process of transferring genetic information from mitochondrial DNA to the complexes of the oxidative phosphorylation system. These synthetases perform an integral step in the initiation of mitochondrial protein synthesis by charging tRNAs with their cognate amino acids. All mtARSs are encoded by nuclear genes, nine of which have recently been described as disease genes for mitochondrial disorders. Unexpectedly, the clinical presentations of these diseases are highly specific to the affected synthetase. Encephalopathy is the most common manifestation but again with gene-specific outcomes. Other clinical presentations include myopathy with anemia, cardiomyopathy, tubulopathy and hearing loss with female ovarian dysgenesis. Here we review the described mutation types and the associated patient phenotypes. The identified mutation spectrum suggests that only mutation types that allow some residual tRNA-charging activity can result in the described mtARS diseases but the molecular mechanisms behind the selective tissue involvement are not currently understood.

Publication types

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

MeSH terms

  • Amino Acyl-tRNA Synthetases / genetics*
  • Amino Acyl-tRNA Synthetases / metabolism
  • Brain Diseases, Metabolic / enzymology
  • Brain Diseases, Metabolic / genetics*
  • DNA, Mitochondrial / genetics
  • Female
  • Hereditary Sensory and Motor Neuropathy / enzymology
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / genetics*
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / genetics
  • Muscular Diseases / enzymology
  • Muscular Diseases / genetics*
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism


  • DNA, Mitochondrial
  • RNA, Transfer
  • Amino Acyl-tRNA Synthetases