Recent Advances in Mitochondrial Aminoacyl-tRNA Synthetases and Disease

Trends Mol Med. 2017 Aug;23(8):693-708. doi: 10.1016/j.molmed.2017.06.002. Epub 2017 Jul 14.


Dysfunctions in mitochondria - the powerhouses of the cell - lead to several human pathologies. Because mitochondria integrate nuclear and mitochondrial genetic systems, they are richly intertwined with cellular activities. The nucleus-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key components of the mitochondrial translation apparatus. Mutations in these enzymes predominantly affect the central nervous system (CNS) but also target other organs. Comparable mutations in mt-aaRSs can lead to vastly diverse diseases, occurring at different stages in life, and within different tissues; this represents a confounding issue. With newer information available, we propose that the pleiotropy and tissue-specificity of mt-aaRS-associated diseases result from the molecular integration of mitochondrial translation events within the cell; namely, through specific crosstalk between the cellular program and the energy demands of the cell. We place particular focus on neuronal cells.

Keywords: aminoacyl-tRNA synthetase; central nervous system; mitochondrial disease; mitochondrial translation; moonlighting proteins; unfolded protein response.

Publication types

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

MeSH terms

  • Amino Acyl-tRNA Synthetases* / genetics
  • Amino Acyl-tRNA Synthetases* / metabolism
  • Animals
  • Humans
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Mitochondria* / pathology
  • Mitochondrial Proteins* / genetics
  • Mitochondrial Proteins* / metabolism
  • Mutation*
  • Nervous System Diseases* / genetics
  • Nervous System Diseases* / metabolism
  • Nervous System Diseases* / pathology
  • Protein Biosynthesis*


  • Mitochondrial Proteins
  • Amino Acyl-tRNA Synthetases