title: Disorders of mitochondrial protein synthesis.
abstract: 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.
authors.affiliation: Institute of Medical Technology, Tampere University Hospital, University of Tampere, Finland. howy.jacobs@uta.fi
authors.forename: Howard T
authors.initials: HT
authors.lastname: Jacobs
mesh_terms: D001483:Base Sequence; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009154:Mutation; D009690:Nucleic Acid Conformation; D012357:RNA, Transfer, Lys / Q000737:chemistry / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D012357:RNA, Transfer, Lys