Role of taurine in the pathologies of MELAS and MERRF
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- 作者：Stephen W. Schaffer (1)
Chian Ju Jong (1)
Takashi Ito (2)
Junichi Azuma (2) - 关键词：Taurine deficiency ; Mitochondrial diseases ; Wobble hypothesis ; Mitochondrial protein synthesis ; Electron transport chain function
- 刊名：Amino Acids
- 出版年：2014
- 出版时间：January 2014
- 年：2014
- 卷：46
- 期：1
- 页码：47-56
- 全文大小：279 KB
- 作者单位：Stephen W. Schaffer (1)
Chian Ju Jong (1)
Takashi Ito (2)
Junichi Azuma (2)
1. Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL, 36688, USA
2. School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan - ISSN：1438-2199
文摘
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.