ArticleEMBO molecular medicine2014
The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.International journal of molecular sciences · 2026Review
- Mitochondrial tRNA-Derived Diseases.International journal of molecular sciences · 2025Review
- Fast, Comprehensive, and User Customizable Macromolecule Interface Analysis with FACE2FACE.Journal of chemical information and modeling · 2025Article
- Mitochondrial tRNA modifications: functions, diseases caused by their loss, and treatment strategies.RNA (New York, N.Y.) · 2025Review
- Peptide-mimetics derived from leucyl-tRNA synthetase are potential agents for the therapy of mt-tRNA related diseases.Frontiers in pharmacology · 2025Article
- Molecular Investigation of Mitochondrial RNA19 Role in the Pathogenesis of MELAS Disease.Life (Basel, Switzerland) · 2023Article
- Restoration of mitochondrial function through activation of hypomodified tRNAs with pathogenic mutations associated with mitochondrial diseases.Nucleic acids research · 2023Article
- Selective degradation of tRNASer(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease.Nucleic acids research · 2022Article
- Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype.Life (Basel, Switzerland) · 2021Article
- The molecular pathology of pathogenic mitochondrial tRNA variants.FEBS letters · 2021Review
- Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNAThe Journal of biological chemistry · 2020Article
- Mitochondrial Dysfunction in Primary Ovarian Insufficiency.Endocrinology · 2019Review
- Mitochondrial DNA transcription and translation: clinical syndromes.Essays in biochemistry · 2018Review
- Emerging therapies for mitochondrial diseases.Essays in biochemistry · 2018Review
- Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease.Nucleic acids research · 2018Article
- Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNAInternational journal of biological sciences · 2018Article
- Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia.Human mutation · 2017Article
- Emerging therapies for mitochondrial disorders.Brain : a journal of neurology · 2016Review
- Short peptides from leucyl-tRNA synthetase rescue disease-causing mitochondrial tRNA point mutations.Human molecular genetics · 2016Article
- A peep into mitochondrial disorder: multifaceted from mitochondrial DNA mutations to nuclear gene modulation.Protein & cell · 2015Review
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 3 countries.
Funding
Abstract
Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNA(Ile) gene. Importantly, we further demonstrate that the carboxy-terminal domain of human mt leucyl-tRNA synthetase is both necessary and sufficient to improve the pathologic phenotype associated either with these "mild" mutations or with the "severe" m.3243A>G mutation in the mt-tRNA(L)(eu(UUR)) gene. Furthermore, we provide evidence that this small, non-catalytic domain is able to directly and specifically interact in vitro with human mt-tRNA(Leu(UUR)) with high affinity and stability and, with lower affinity, with mt-tRNA(Ile). Taken together, our results sustain the hypothesis that the carboxy-terminal domain of human mt leucyl-tRNA synthetase can be used to correct mt dysfunctions caused by mt-tRNA mutations.
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