Background Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) is a group of genetic diseases caused by mutations in mitochondrial DNA and nuclear DNA. The causative mutations of MELAS have drawn much attention, among them, mutations in mitochondrial tRNA genes possessing prominent status. However, the detailed molecular pathogenesis of these tRNA gene mutations remains unclear and there are very few effective therapies available to date.

Methods We performed muscle histochemistry, genetic analysis, molecular dynamic stimulation and measurement of oxygen consumption rate and respiratory chain complex activities to demonstrate the molecular pathomechanisms of m.5541C>T mutation. Moreover, we use cybrid cells to investigate the potential of taurine to rescue mitochondrial dysfunction caused by this mutation.

Results We found a pathogenic m.5541C>T mutation in the tRNA^Trp gene in a large MELAS family. This mutation first affected the maturation and stability of tRNA^Trp and impaired mitochondrial respiratory chain complex activities, followed by remarkable mitochondrial dysfunction. Surprisingly, we identified that the supplementation of taurine almost completely restored mitochondrial tRNA^Trp levels and mitochondrial respiration deficiency at the in vitro cell level.

Conclusion The m.5541C>T mutation disturbed the translation machinery of mitochondrial tRNA^Trp and taurine supplementation may be a potential treatment for patients with m.5541C>T mutation. Further studies are needed to explore the full potential of taurine supplementation as therapy for patients with this mutation.