ArticleMolecular and cellular biology2010
Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 133 citations in OpenAlex.
- Mitochondrial DNA A3243G variant: Current perspectives and clinical implications.Intractable & rare diseases research · 2025Review
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- The Role and Research Progress of Mitochondria in Sensorineural Hearing Loss.Molecular neurobiology · 2025Review
- Peptide-mimetics derived from leucyl-tRNA synthetase are potential agents for the therapy of mt-tRNA related diseases.Frontiers in pharmacology · 2025Article
- Comprehensive phenotypic assessment of nonsense mutations in mitochondrial ND5 in mice.Experimental & molecular medicine · 2024Article
- Post-transcriptional methylation of mitochondrial-tRNA differentially contributes to mitochondrial pathology.Nature communications · 2024Article
- Mitochondrial Dysfunction and Imeglimin: A New Ray of Hope for the Treatment of Type-2 Diabetes Mellitus.Mini reviews in medicinal chemistry · 2024Review
- Clinical Approaches for Mitochondrial Diseases.Cells · 2023Review
- Multi-Organ Nutrigenomic Effects of Dietary Grapes in a Mouse Model.Antioxidants (Basel, Switzerland) · 2023Article
- Induced pluripotent stem cells: ex vivo models for human diseases due to mitochondrial DNA mutations.Journal of biomedical science · 2023Review
- Restoration of mitochondrial function through activation of hypomodified tRNAs with pathogenic mutations associated with mitochondrial diseases.Nucleic acids research · 2023Article
- Optimized allotopic expression of mitochondrial ND6 transgene restored complex I and apoptosis deficiencies caused by LHON-linked ND6 14484T > C mutation.Journal of biomedical science · 2023Article
- Multimodal single-cell analysis of nonrandom heteroplasmy distribution in human retinal mitochondrial disease.JCI insight · 2023Article
- Mitochondria dysfunction and bipolar disorder: From pathology to therapy.IBRO neuroscience reports · 2023Article
- Small molecule agonist of mitochondrial fusion repairs mitochondrial dysfunction.Nature chemical biology · 2023Article
- Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis.Current neuropharmacology · 2023Review
- Selective degradation of tRNASer(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease.Nucleic acids research · 2022Article
- Associations between forensic loci and expression levels of neighboring genes may compromise medical privacy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genotype-phenotype correlation in IARS2-related diseases: A case report and review of literature.Clinical case reports · 2022Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in mitochondrial tRNA genes are associated with a wide spectrum of human diseases. In particular, the tRNA(Leu(UUR)) A3243G mutation causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms (MELAS) and 2% of cases of type 2 diabetes. The primary defect in this mutation was an inefficient aminoacylation of the tRNA(Leu(UUR)). In the present study, we have investigated the molecular mechanism of the A3243G mutation and whether the overexpression of human mitochondrial leucyl-tRNA synthetase (LARS2) in the cytoplasmic hybrid (cybrid) cells carrying the A3243G mutation corrects the mitochondrial dysfunctions. Human LARS2 localizes exclusively to mitochondria, and LARS2 is expressed ubiquitously but most abundantly in tissues with high metabolic rates. We showed that the alteration of aminoacylation tRNA(Leu(UUR)) caused by the A3243G mutation led to mitochondrial translational defects and thereby reduced the aminoacylated efficiencies of tRNA(Leu(UUR)) as well as tRNA(Ala) and tRNA(Met). We demonstrated that the transfer of human mitochondrial leucyl-tRNA synthetase into the cybrid cells carrying the A3243G mutation improved the efficiency of aminoacylation and stability of mitochondrial tRNAs and then increased the rates of mitochondrial translation and respiration, consequently correcting the mitochondrial dysfunction. These findings provide new insights into the molecular mechanism of maternally inherited diseases and a step toward therapeutic interventions for these disorders.
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