Fig. 2. Comparison of MELAS and taurine deficiency in mitochondria. The mitochondrial disease, MELAS, is caused by specific point mutations in mitochondrial DNA (mtDNA) that codes for tRNALeu(UUR). Most of the point mutations of MELAS with 80% frequency occur at A3243G while mutations at T3271C exist with 10% frequency. In mtDNA, ND genes are shown in red color and tRNA genes are depicted as blue circles. The gene of tRNALeu(UUR) responsible for MELAS is located adjacent to ND1. The mutation in MELAS alters the structure of the tRNALeu(UUR) preventing the conjugation of taurine with the uridine base of the UAA anti-codon from forming 5-taurinomethyluridine (τm5U). MELAS patients also show reduced aminoacylation of taurine deficient tRNALeu(UUR) by leucine catalyzed by aminoacyl-tRNA synthetase (AS). Both reduced aminoacylation of tRNALeu(UUR) by leucine and formation of the taurine conjugate of τm5UAA-tRNALeu(UUR) prevent decoding of mitochondrial UUG-dependent proteins, including ND6, which is one of 44 protein subunits of complex I of the electron transport chain located in the mitochondria inner membrane. On the other hand, taurine deficiency has normal aminoacylation of tRNALeu(UUR) by leucine, but exhibits reduced formation of the taurine conjugate of τm5UAA-tRNALeu(UUR), which also prevents decoding of mitochondrial ND6 mRNA, resulting in increased superoxide generation and reduced ATP generation. MELAS: mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; ND6: NADH-ubiquinone oxidoreductase chain 6; mt IS: motochodrial intermembrane space; mtIM: mitochondrial inner membrane; LS: light strand; HS: heavy strand.
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