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Mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial tRNA(Met) 4467 C>A mutation in a Han Chinese family with maternally inherited hypertension

To investigate the relationship between mitochondrial DNA (mtDNA) and hypertension as well as the mechanism involved in mitochondrial metabolic dysfunction. We identified a novel tRNA(Met) C4467A mutation in a Han Chinese family with hypertension. The maternal members presented with increased glucos...

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Autores principales: Liu, Yuqi, Li, Yang, Zhu, Chao, Tian, Liuyang, Guan, Minxin, Chen, Yundai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465199/
https://www.ncbi.nlm.nih.gov/pubmed/28596595
http://dx.doi.org/10.1038/s41598-017-03303-w
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author Liu, Yuqi
Li, Yang
Zhu, Chao
Tian, Liuyang
Guan, Minxin
Chen, Yundai
author_facet Liu, Yuqi
Li, Yang
Zhu, Chao
Tian, Liuyang
Guan, Minxin
Chen, Yundai
author_sort Liu, Yuqi
collection PubMed
description To investigate the relationship between mitochondrial DNA (mtDNA) and hypertension as well as the mechanism involved in mitochondrial metabolic dysfunction. We identified a novel tRNA(Met) C4467A mutation in a Han Chinese family with hypertension. The maternal members presented with increased glucose, total cholesterol, low-density lipoprotein, and serum sodium as well as decreased potassium compared with non-maternal members (P < 0.05). Segregation analysis showed this mutation was maternally inherited. We analyzed lymphocyte cell lines derived from three maternal and three non-maternal family members. Reactive oxygen species production in the mutant cell lines was 114.5% higher compared with that in controls (P < 0.05) while ATP was 26.4% lower. The mitochondrial membrane potential of the mutated cell lines was 26.2% lower than that in controls (P < 0.05). Oxygen consumption rates were decreased in the mutant cell lines (P < 0.05). The activation of caspase-3/7 was 104.1% higher in the mutant cell lines compared with controls (P < 0.05). The expression of voltage-dependent anion channel (VDAC), Bax and apoptosis-inducing factor (AIF) in the mutant cell lines was higher compared with that in controls, with the increased colocalization of VDAC and Bax. Therefore, this mutation contributes to oxidative stress and mitochondrial biogenesis dysfunction, which may be involved in the pathogenesis of hypertension.
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spelling pubmed-54651992017-06-14 Mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial tRNA(Met) 4467 C>A mutation in a Han Chinese family with maternally inherited hypertension Liu, Yuqi Li, Yang Zhu, Chao Tian, Liuyang Guan, Minxin Chen, Yundai Sci Rep Article To investigate the relationship between mitochondrial DNA (mtDNA) and hypertension as well as the mechanism involved in mitochondrial metabolic dysfunction. We identified a novel tRNA(Met) C4467A mutation in a Han Chinese family with hypertension. The maternal members presented with increased glucose, total cholesterol, low-density lipoprotein, and serum sodium as well as decreased potassium compared with non-maternal members (P < 0.05). Segregation analysis showed this mutation was maternally inherited. We analyzed lymphocyte cell lines derived from three maternal and three non-maternal family members. Reactive oxygen species production in the mutant cell lines was 114.5% higher compared with that in controls (P < 0.05) while ATP was 26.4% lower. The mitochondrial membrane potential of the mutated cell lines was 26.2% lower than that in controls (P < 0.05). Oxygen consumption rates were decreased in the mutant cell lines (P < 0.05). The activation of caspase-3/7 was 104.1% higher in the mutant cell lines compared with controls (P < 0.05). The expression of voltage-dependent anion channel (VDAC), Bax and apoptosis-inducing factor (AIF) in the mutant cell lines was higher compared with that in controls, with the increased colocalization of VDAC and Bax. Therefore, this mutation contributes to oxidative stress and mitochondrial biogenesis dysfunction, which may be involved in the pathogenesis of hypertension. Nature Publishing Group UK 2017-06-08 /pmc/articles/PMC5465199/ /pubmed/28596595 http://dx.doi.org/10.1038/s41598-017-03303-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Yuqi
Li, Yang
Zhu, Chao
Tian, Liuyang
Guan, Minxin
Chen, Yundai
Mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial tRNA(Met) 4467 C>A mutation in a Han Chinese family with maternally inherited hypertension
title Mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial tRNA(Met) 4467 C>A mutation in a Han Chinese family with maternally inherited hypertension
title_full Mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial tRNA(Met) 4467 C>A mutation in a Han Chinese family with maternally inherited hypertension
title_fullStr Mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial tRNA(Met) 4467 C>A mutation in a Han Chinese family with maternally inherited hypertension
title_full_unstemmed Mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial tRNA(Met) 4467 C>A mutation in a Han Chinese family with maternally inherited hypertension
title_short Mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial tRNA(Met) 4467 C>A mutation in a Han Chinese family with maternally inherited hypertension
title_sort mitochondrial biogenesis dysfunction and metabolic dysfunction from a novel mitochondrial trna(met) 4467 c>a mutation in a han chinese family with maternally inherited hypertension
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465199/
https://www.ncbi.nlm.nih.gov/pubmed/28596595
http://dx.doi.org/10.1038/s41598-017-03303-w
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