Human Molecular Genetics Advance Access originally published online on August 19, 2003
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Human Molecular Genetics, 2003, Vol. 12, Review Issue 2 R293-R301
DOI: 10.1093/hmg/ddg285
© 2003 Oxford University Press
Disorders of mitochondrial protein synthesis
Institute of Medical Technology and Tampere University Hospital, University of Tampere, Finland and Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK
Received August 7, 2003; Accepted August 13, 2003
Mitochondrial tRNA gene mutations, including heteroplasmic deletions that eliminate one or more tRNAs, as well as point mutations that may be either hetero- or homoplasmic, are associated with a wide spectrum of human diseases. These range from rare syndromic disorders to cases of commoner conditions such as sensorineural deafness or cardiomyopathy. The disease spectrum of mutations in a given gene, or even a single mutation, may vary, but some patterns are evident, for example the prominence of cardiomyopathy resulting from tRNAIle defects, or of MERFF-like disease from tRNALys defects. Molecular studies of many laboratories have reached a consensus on molecular mechanisms associated with these mutations. Although precise details vary, loss of translational function of the affected tRNA(s) seems to be the final outcome, whether by impaired pre-tRNA processing, half-life, base-modification or aminoacylation. However, a mechanistic understanding of the consequences of this for the assembly and function of the mitochondrial OXPHOS complexes and for the physiological functions of the affected tissues is still a distant prospect. This review presents some views of possible downstream consequences of specific tRNA deficiencies.
* To whom correspondence should be addressed at: Institute of Medical Technology, FIN-33014 University of Tampere, Finland. Tel: +358 32157731; Fax: +358 32157710; E-mail: howy.jacobs{at}uta.fi
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