A mitochondrial myopathy-associated tRNASer(UCN) 7453G>A mutation alters tRNA metabolism and mitochondrial function

Background: Mitochondrial disorders are a group of heterogeneous diseases characterized by biochemical disturbances in oxidative phosphorylation (OXPHOS). Mutations in mitochondrial transfer RNA (mt-tRNA) genes are the most frequently in mitochondrial disease. However, few studies have detailed the molecular mechanisms behind these mutations. Methods: We performed clinical evaluation, genetic analysis, muscle histochemistry, and molecular and biochemical investigations in muscle tissue and proband-derived cybrid cell lines. Results: We found a mitochondrial tRNA(Ser(UCN)) mutation (m.7453G>A) in a 15-year-old patient with severe mitochondrial myopathy. We demonstrated that this mutation caused impairment of mitochondrial translation, respiratory deficiency, overproduction of reactive oxygen species (ROS), and decreased mitochondrial membrane potential (MMP), which ultimately led to severe mitochondrial myopathy. Conclusion: Our findings offer valuable new insights into the tRNA(Ser(UCN)) m.7453G>A mutation for both the pathogenic mechanism and functional consequences.

Automated summary

This study identified a mitochondrial tRNA(Ser(UCN)) mutation causing severe mitochondrial myopathy, leading to impaired mitochondrial translation, respiratory deficiency, ROS overproduction, and decreased MMP. These findings offer valuable insights into the pathogenic mechanism and functional consequences of the mt-tRNA mutation.