Correction of Translational Defects in Patient-derived Mutant Mitochondria by Complex-mediated Import of a Cytoplasmic tRNA*
- Genetic Engineering Laboratory, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 7000032, India
- ↵§ To whom correspondence should be addressed. Tel.: 91-33-2473-3491 (ext. 136); Fax: 91-33-2472-3967; E-mail: sadhya{at}iicb.res.in.
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 
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 tRNALys 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.
- Received December 10, 2004.
- Revision received December 23, 2004.
- The American Society for Biochemistry and Molecular Biology, Inc.
