title: Correction of translational defects in patient-derived mutant mitochondria by complex-mediated import of a cytoplasmic tRNA.
abstract: 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.
authors.affiliation: Genetic Engineering Laboratory, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 7000032, India.
authors.forename: Bidesh
authors.initials: B
authors.lastname: Mahata
authors.forename: Suvendra Nath
authors.initials: SN
authors.lastname: Bhattacharyya
authors.forename: Saikat
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Samit
authors.initials: S
authors.lastname: Adhya
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics / Q000473:pathology; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics / Q000473:pathology; D007891:Leishmania; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D046912:Multiprotein Complexes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D015800:Protozoan Proteins / Q000378:metabolism*; D034443:RNA Transport; D012357:RNA, Transfer, Lys / Q000235:genetics / Q000378:metabolism*; D046249:Transfer RNA Aminoacylation
chemical_list: D046912:Multiprotein Complexes; D015800:Protozoan Proteins; D012357:RNA, Transfer, Lys; D000255:Adenosine Triphosphate