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Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNA(Ala) mutation in cybrids
Mutations of mitochondrial transfer RNAs (mt-tRNAs) play a major role in a wide range of mitochondrial diseases because of the vital role of these molecules in mitochondrial translation. It has previously been reported that the overexpression of mitochondrial aminoacyl tRNA synthetases is effective...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158735/ https://www.ncbi.nlm.nih.gov/pubmed/30262995 http://dx.doi.org/10.7150/ijbs.27043 |
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author | Zhao, Xiaoxu Han, Jiamin Zhu, Ling Xiao, Yun Wang, Chenghui Hong, Fang Jiang, Pingping Guan, Min-Xin |
author_facet | Zhao, Xiaoxu Han, Jiamin Zhu, Ling Xiao, Yun Wang, Chenghui Hong, Fang Jiang, Pingping Guan, Min-Xin |
author_sort | Zhao, Xiaoxu |
collection | PubMed |
description | Mutations of mitochondrial transfer RNAs (mt-tRNAs) play a major role in a wide range of mitochondrial diseases because of the vital role of these molecules in mitochondrial translation. It has previously been reported that the overexpression of mitochondrial aminoacyl tRNA synthetases is effective at partially suppressing the defects resulting from mutations in their cognate mt-tRNAs in cells. Here we report a detailed analysis of the suppressive activities of mitochondrial alanyl-tRNA synthetase (AARS2) on mt-tRNA(Ala) 5655 A>G mutant. Mitochondrial defects in respiration, activity of oxidative phosphorylation complexes, ATP production, mitochondrial superoxide, and membrane potential were consistently rescued in m.5655A>G cybrids upon AARS2 expression. However, AARS2 overexpression did not result in a detectable increase in mutated mt-tRNA(Ala) but caused an increase incharged mt-tRNA(Ala) in mutant cybrids, leading to enhanced mitochondrial translation. This indicated that AARS2 improved the aminoacylation activity in the case of m.5655A>G, rather than having a stabilizing effect on the tRNA structure. The data presented in this paper deepen our understanding of the pathogenesis of mt-tRNA diseases. |
format | Online Article Text |
id | pubmed-6158735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-61587352018-09-27 Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNA(Ala) mutation in cybrids Zhao, Xiaoxu Han, Jiamin Zhu, Ling Xiao, Yun Wang, Chenghui Hong, Fang Jiang, Pingping Guan, Min-Xin Int J Biol Sci Research Paper Mutations of mitochondrial transfer RNAs (mt-tRNAs) play a major role in a wide range of mitochondrial diseases because of the vital role of these molecules in mitochondrial translation. It has previously been reported that the overexpression of mitochondrial aminoacyl tRNA synthetases is effective at partially suppressing the defects resulting from mutations in their cognate mt-tRNAs in cells. Here we report a detailed analysis of the suppressive activities of mitochondrial alanyl-tRNA synthetase (AARS2) on mt-tRNA(Ala) 5655 A>G mutant. Mitochondrial defects in respiration, activity of oxidative phosphorylation complexes, ATP production, mitochondrial superoxide, and membrane potential were consistently rescued in m.5655A>G cybrids upon AARS2 expression. However, AARS2 overexpression did not result in a detectable increase in mutated mt-tRNA(Ala) but caused an increase incharged mt-tRNA(Ala) in mutant cybrids, leading to enhanced mitochondrial translation. This indicated that AARS2 improved the aminoacylation activity in the case of m.5655A>G, rather than having a stabilizing effect on the tRNA structure. The data presented in this paper deepen our understanding of the pathogenesis of mt-tRNA diseases. Ivyspring International Publisher 2018-08-06 /pmc/articles/PMC6158735/ /pubmed/30262995 http://dx.doi.org/10.7150/ijbs.27043 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Zhao, Xiaoxu Han, Jiamin Zhu, Ling Xiao, Yun Wang, Chenghui Hong, Fang Jiang, Pingping Guan, Min-Xin Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNA(Ala) mutation in cybrids |
title | Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNA(Ala) mutation in cybrids |
title_full | Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNA(Ala) mutation in cybrids |
title_fullStr | Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNA(Ala) mutation in cybrids |
title_full_unstemmed | Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNA(Ala) mutation in cybrids |
title_short | Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNA(Ala) mutation in cybrids |
title_sort | overexpression of human mitochondrial alanyl-trna synthetase suppresses biochemical defects of the mt-trna(ala) mutation in cybrids |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158735/ https://www.ncbi.nlm.nih.gov/pubmed/30262995 http://dx.doi.org/10.7150/ijbs.27043 |
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