Taurine Deficiency and MELAS Are Closely Related Syndromes

Abstract

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is a mitochondrial disease caused by one or more mutations of tRNA(Leu(UUR)). These mutations reduce both the aminoacylation of tRNA(Leu(UUR)) and a posttranslational modification in the wobble position of tRNA(Leu(UUR)). Both changes result in reduced transcription of mitochondria-encoded proteins; however, reduced aminoacylation affects the decoding of both UUG and UUA while the wobble defect specifically diminishes UUG decoding. Because 12 out of the 13 mitochondria-encoded proteins are more dependent on UUA decoding than UUG decoding, the aminoacylation defect should have a more profound effect on protein synthesis than the wobble defect, which more specifically alters the expression of one mitochondria-encoded protein, ND6. Taurine serves as a substrate in the formation of 5-taurinomethyluridine-tRNA(Leu(UUR)); therefore, taurine deficiency should mimic 5-taurinomethyluridine-tRNA(Leu(UUR)) deficiency. Hence, the wobble hypothesis predicts that the symptoms of MELAS mimic those of taurine deficiency, provided that the dominant defect in MELAS is wobble modification deficiency. On the other hand, if the aminoacylation defect dominates, significant differences should exist between taurine deficiency and MELAS. The present review tests this hypothesis by comparing the symptoms of MELAS and taurine deficiency.