title: Role of taurine in the pathologies of MELAS and MERRF.
abstract: Taurine is an abundant β-amino acid that concentrates in the mitochondria, where it participates in the conjugation of tRNAs for leucine, lysine, glutamate and glutamine. The formation of 5-taurinomethyluridine-tRNA strengthens the interaction of the anticodon with the codon, thereby promoting the decoding of several codons, including those for AAG, UUG, CAG and GAG. By preventing these series of events, taurine deficiency appears to diminish the formation of 5-taurinomethyluridine and causes inefficient decoding for the mitochondrial codons of leucine, lysine, glutamate and glutamine. The resulting reduction in the biosynthesis of mitochondria-encoded proteins deprives the respiratory chain of subunits required for the assembly of respiratory chain complexes. Hence, taurine deficiency is associated with a reduction in oxygen consumption, an elevation in glycolysis and lactate production and a decline in ATP production. A similar sequence of events takes place in mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fiber syndrome). In both diseases, mutations in their respective tRNAs interfere with the formation of 5-taurinomethyluridine in the wobble position. Hence, the taurine-deficient phenotype resembles the phenotypes of MELAS and MERRF.
authors.affiliation: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL, 36688, USA, sschaffe@southalabama.edu.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Schaffer
authors.forename: Chian Ju
authors.initials: CJ
authors.lastname: Jong
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
mesh_terms: D000818:Animals; D018388:Codon, Terminator / Q000235:genetics / Q000378:metabolism; D004579:Electron Transport / Q000235:genetics; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D017243:MERRF Syndrome / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D013654:Taurine / Q000235:genetics / Q000378:metabolism*; D014529:Uridine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism
chemical_list: C522070:5-taurinomethyluridine; D018388:Codon, Terminator; D024101:Mitochondrial Proteins; D013654:Taurine; D012343:RNA, Transfer; D014529:Uridine