Taurine Deficiency and MELAS Are Closely Related Syndromes - Advances in Experimental Medicine and Biology - page 142

Chapter 16
Taurine Deficiency and MELAS Are Closely
Related Syndromes
Stephen W. Schaffer , Chian Ju Jong , Danielle Warner , Takashi Ito ,
and Junichi Azuma
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; how-
ever, 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.
S. W. Schaffer ( * ) ￿ C. J. Jong ￿ D. Warner
Department of Pharmacology, School of Medicine, University of South Alabama,
Mobile , AL , USA
e-mail: [e-mail]
T. Ito ￿ J. Azuma
Hyogo University of Health Sciences, School of Pharmacy , Kobe , Japan