ArticleMolecular and cellular biology2016
A Hypertension-Associated tRNAAla Mutation Alters tRNA Metabolism and Mitochondrial Function.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- Mitochondrial cardiovascular diseases: molecular mechanisms, multi-omics exploration and therapeutic strategies.Journal of advanced research · 2026Review
- Mitochondrial tRNAAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Loss of MTX2 causes mitochondrial dysfunction, podocyte injury, nephrotic proteinuria and glomerulopathy in mice and patients.International journal of biological sciences · 2024Article
- Mitochondrial Diabetes Is Associated with theBiomolecules · 2023Article
- Novel mitochondrial tRNAIrish journal of medical science · 2023Article
- Decorin evokes reversible mitochondrial depolarization in carcinoma and vascular endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Mitochondrial mutations in protein coding genes of respiratory chain including complexes IV, V, and mt-tRNA genes are associated risk factors for congenital heart disease.EXCLI journal · 2022Article
- Assocation Between Leber's Hereditary Optic Neuropathy and MT-ND1 3460G>A Mutation-Induced Alterations in Mitochondrial Function, Apoptosis, and Mitophagy.Investigative ophthalmology & visual science · 2021Article
- Leber's Hereditary Optic Neuropathy Arising From the Synergy Between ND1 3635G>A Mutation and Mitochondrial YARS2 Mutations.Investigative ophthalmology & visual science · 2021Article
- Disease-associated mutations in mitochondrial precursor tRNAs affect binding, m1R9 methylation, and tRNA processing by mtRNase P.RNA (New York, N.Y.) · 2021Article
- Mutational Analysis of Mitochondrial tRNA Genes in 200 Patients with Type 2 Diabetes Mellitus.International journal of general medicine · 2021Article
- mtDNA in the Pathogenesis of Cardiovascular Diseases.Disease markers · 2021Article
- Asymmetrical effects of deafness-associated mitochondrial DNA 7516delA mutation on the processing of RNAs in the H-strand and L-strand polycistronic transcripts.Nucleic acids research · 2020Article
- Complex I mutations synergize to worsen the phenotypic expression of Leber's hereditary optic neuropathy.The Journal of biological chemistry · 2020Article
- Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNAThe Journal of biological chemistry · 2020Article
- Mitochondrial tRNA Mutations Associated With Essential Hypertension: From Molecular Genetics to Function.Frontiers in cell and developmental biology · 2020Review
- tRNA-Derived Small RNAs and Their Potential Roles in Cardiac Hypertrophy.Frontiers in pharmacology · 2020Review
- Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation.BMC cardiovascular disorders · 2019Article
- Contribution of a mitochondrial tyrosyl-tRNA synthetase mutation to the phenotypic expression of the deafness-associated tRNAThe Journal of biological chemistry · 2019Article
- Hypertension-associated mitochondrial DNA 4401A>G mutation caused the aberrant processing of tRNAMet, all 8 tRNAs and ND6 mRNA in the light-strand transcript.Nucleic acids research · 2019Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this report, we investigated the pathophysiology of a novel hypertension-associated mitochondrial tRNA(Ala) 5655A → G (m.5655A → G) mutation. The destabilization of a highly conserved base pairing (A1-U72) at the aminoacyl acceptor stem by an m.5655A → G mutation altered the tRNA(Ala) function. An in vitro processing analysis showed that the m.5655A → G mutation reduced the efficiency of tRNA(Ala) precursor 5' end cleavage catalyzed by RNase P. By using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from a Chinese family into mitochondrial DNA (mtDNA)-less (ρ(o)) cells, we showed a 41% reduction in the steady-state level of tRNA(Ala) in mutant cybrids. The mutation caused an improperly aminoacylated tRNA(Ala), as suggested by aberrantly aminoacylated tRNA(Ala) and slower electrophoretic mobility of mutated tRNA. A failure in tRNA(Ala) metabolism contributed to variable reductions in six mtDNA-encoded polypeptides in mutant cells, ranging from 21% to 37.5%, with an average of a 29.1% reduction, compared to levels of the controls. The impaired translation caused reduced activities of mitochondrial respiration chains. Furthermore, marked decreases in the levels of mitochondrial ATP and membrane potential were observed in mutant cells. These caused increases in the production of reactive oxygen species in the mutant cybrids. The data provide evidence for the association of the tRNA(Ala) 5655A → G mutation with hypertension.
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