ArticleNucleic acids research2023
Restoration of mitochondrial function through activation of hypomodified tRNAs with pathogenic mutations associated with mitochondrial diseases.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 25 citations in OpenAlex.
- Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.International journal of molecular sciences · 2026Review
- Molecular pathogenesis and gene therapy-based intervention of GTPBP3-related mitochondrial disease.Nature communications · 2026Article
- Small but mighty: mitochondrial DNA at the centre of retrograde signalling.Cell communication and signaling : CCS · 2026Review
- Roles and related underlying mechanisms of mitochondrial RNA modification in cancer progression.Acta pharmacologica Sinica · 2026Review
- Uridines Modified with Sulfur or Selenium in U-G Wobble Pairs Matter for tRNA Function.Current medicinal chemistry · 2026Review
- Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.Frontiers in immunology · 2026Review
- Mitochondrial tRNA-Derived Diseases.International journal of molecular sciences · 2025Review
- Mitochondrial tRNA modifications: functions, diseases caused by their loss, and treatment strategies.RNA (New York, N.Y.) · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Diagnostic challenges in mitochondrial encephalomyopathy with m.10158T>C mutation: a case report and literature review.Frontiers in integrative neuroscience · 2025Article
- Post-transcriptional methylation of mitochondrial-tRNA differentially contributes to mitochondrial pathology.Nature communications · 2024Article
- Queuine ameliorates impaired mitochondrial function caused by mt-tRNAJournal of translational medicine · 2024Article
- tRNA Modifications and Dysregulation: Implications for Brain Diseases.Brain sciences · 2024Review
- Structural basis for human mitochondrial tRNA maturation.Nature communications · 2024Article
- Advances in the Structural and Functional Understanding of mAccounts of chemical research · 2024Article
- Progressive Myoclonus Epilepsy: A Scoping Review of Diagnostic, Phenotypic and Therapeutic Advances.Genes · 2024Article
- A clinical approach to diagnosis and management of mitochondrial myopathies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Dietary Taurine Improves Growth Performance and Intestine Health via the GSH/GSSG Antioxidant System and Nrf2/ARE Signaling Pathway in Weaned Piglets.Antioxidants (Basel, Switzerland) · 2023Article
- Mitochondrial haplotype mutation alleviates respiratory defect of MELAS by restoring taurine modification in tRNA with 3243A > G mutation.Nucleic acids research · 2023Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in mitochondrial (mt-)tRNAs frequently cause mitochondrial dysfunction. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and myoclonus epilepsy associated with ragged red fibers (MERRF) are major clinical subgroups of mitochondrial diseases caused by pathogenic point mutations in tRNA genes encoded in mtDNA. We previously reported a severe reduction in the frequency of 5-taurinomethyluridine (τm5U) and its 2-thiouridine derivative (τm5s2U) in the anticodons of mutant mt-tRNAs isolated from the cells of patients with MELAS and MERRF, respectively. The hypomodified tRNAs fail to decode cognate codons efficiently, resulting in defective translation of respiratory chain proteins in mitochondria. To restore the mitochondrial activity of MELAS patient cells, we overexpressed MTO1, a τm5U-modifying enzyme, in patient-derived myoblasts. We used a newly developed primer extension method and showed that MTO1 overexpression almost completely restored the τm5U modification of the MELAS mutant mt-tRNALeu(UUR). An increase in mitochondrial protein synthesis and oxygen consumption rate suggested that the mitochondrial function of MELAS patient cells can be activated by restoring the τm5U of the mutant tRNA. In addition, we confirmed that MTO1 expression restored the τm5s2U of the mutant mt-tRNALys in MERRF patient cells. These findings pave the way for epitranscriptomic therapies for mitochondrial diseases.
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