Correction of translational defects in patient-derived mutant mitochondria by complex-mediated import of a cytoplasmic tRNA

J Biol Chem. 2005 Feb 18;280(7):5141-4. doi: 10.1074/jbc.C400572200. Epub 2004 Dec 24.


A variety of clinical disorders result from mutations in mitochondrial tRNA genes, leading to translational defects. We show here that a protein complex from the kinetoplastid protozoon Leishmania induces specific, ATP-dependent import of human cytoplasmic tRNA(1)(Lys) into human mitochondria in vitro. The imported tRNA undergoes efficient aminoacylation within the organelle and supports organellar protein synthesis. Moreover, translation in mitochondria from patients with myclonic epilepsy with ragged red fibers (MERRF) and Kearns-Sayre syndrome (KSS), containing mutant tRNA(Lys) genes, is stimulated to near-wild-type levels and the formation of aberrant polypeptides suppressed by complex-mediated import. These results suggest a novel way to introduce RNAs for the modulation of mitochondrial gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cytoplasm / genetics*
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Humans
  • Kearns-Sayre Syndrome / genetics
  • Kearns-Sayre Syndrome / pathology
  • Leishmania
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Multiprotein Complexes / metabolism
  • Protein Biosynthesis / genetics*
  • Protozoan Proteins / metabolism*
  • RNA Transport*
  • RNA, Transfer, Lys / genetics
  • RNA, Transfer, Lys / metabolism*
  • Transfer RNA Aminoacylation


  • Multiprotein Complexes
  • Protozoan Proteins
  • RNA, Transfer, Lys
  • Adenosine Triphosphate