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Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation

BACKGROUND: Coronary heart disease (CHD) is the most common cause of mortality globally, yet mitochondrial genetic mutations associated with CHD development remain incompletely understood. METHODS: The subjects from three Chinese families with LHON underwent clinical, genetic, molecular, and biochem...

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Autores principales: Zhang, Zhenxiao, Liu, Mingyang, He, Jianshuai, Zhang, Xiaotian, Chen, Yuehua, Li, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912950/
https://www.ncbi.nlm.nih.gov/pubmed/31842766
http://dx.doi.org/10.1186/s12872-019-01284-4
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author Zhang, Zhenxiao
Liu, Mingyang
He, Jianshuai
Zhang, Xiaotian
Chen, Yuehua
Li, Hui
author_facet Zhang, Zhenxiao
Liu, Mingyang
He, Jianshuai
Zhang, Xiaotian
Chen, Yuehua
Li, Hui
author_sort Zhang, Zhenxiao
collection PubMed
description BACKGROUND: Coronary heart disease (CHD) is the most common cause of mortality globally, yet mitochondrial genetic mutations associated with CHD development remain incompletely understood. METHODS: The subjects from three Chinese families with LHON underwent clinical, genetic, molecular, and biochemical evaluations. Biochemical characterizations included measuring the effects of the15910C > T mutation on tRNA(Thr) levels, enzymatic activity of electron transport chain complexes, membrane permeability, and the mitochondria-mediated generation of both reactive oxygen species (ROS) and adenosine triphosphate (ATP). RESULTS: We characterize mitochondrial genetic mutations in a three-generation Chinese family exhibiting signs of maternally inherited CHD. Of the 24 different family members in this pedigree we assessed, CHD was detected in 6, with variable severity and age of first appearance. When we sequenced the mitochondrial genomes of these individuals, we found a tRNA(Thr) 15910C > T mutation of the Eastern Asian haplogroup M7b’c. This mutation is predicted to destabilize the strongly conserved (24C-10G) base-pairing, thereby disrupting tRNA(Thr) functionality. When we performed Northern blotting, we detected we observed a 37.5% reduction in tRNA(Thr) levels at baseline in cybrid cell lines bearing the 15910C > T mutation. When we conducted western blot analysis, we detected a ~ 24.96% decrease in mitochondrial translation rates in these same cells. CONCLUSIONS: In the present report, Together these findings suggest a possible link between this 15910C > T tRNA(Thr) mutation and CHD, potentially offering new avenues for future disease intervention.
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spelling pubmed-69129502019-12-30 Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation Zhang, Zhenxiao Liu, Mingyang He, Jianshuai Zhang, Xiaotian Chen, Yuehua Li, Hui BMC Cardiovasc Disord Research Article BACKGROUND: Coronary heart disease (CHD) is the most common cause of mortality globally, yet mitochondrial genetic mutations associated with CHD development remain incompletely understood. METHODS: The subjects from three Chinese families with LHON underwent clinical, genetic, molecular, and biochemical evaluations. Biochemical characterizations included measuring the effects of the15910C > T mutation on tRNA(Thr) levels, enzymatic activity of electron transport chain complexes, membrane permeability, and the mitochondria-mediated generation of both reactive oxygen species (ROS) and adenosine triphosphate (ATP). RESULTS: We characterize mitochondrial genetic mutations in a three-generation Chinese family exhibiting signs of maternally inherited CHD. Of the 24 different family members in this pedigree we assessed, CHD was detected in 6, with variable severity and age of first appearance. When we sequenced the mitochondrial genomes of these individuals, we found a tRNA(Thr) 15910C > T mutation of the Eastern Asian haplogroup M7b’c. This mutation is predicted to destabilize the strongly conserved (24C-10G) base-pairing, thereby disrupting tRNA(Thr) functionality. When we performed Northern blotting, we detected we observed a 37.5% reduction in tRNA(Thr) levels at baseline in cybrid cell lines bearing the 15910C > T mutation. When we conducted western blot analysis, we detected a ~ 24.96% decrease in mitochondrial translation rates in these same cells. CONCLUSIONS: In the present report, Together these findings suggest a possible link between this 15910C > T tRNA(Thr) mutation and CHD, potentially offering new avenues for future disease intervention. BioMed Central 2019-12-16 /pmc/articles/PMC6912950/ /pubmed/31842766 http://dx.doi.org/10.1186/s12872-019-01284-4 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhang, Zhenxiao
Liu, Mingyang
He, Jianshuai
Zhang, Xiaotian
Chen, Yuehua
Li, Hui
Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation
title Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation
title_full Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation
title_fullStr Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation
title_full_unstemmed Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation
title_short Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation
title_sort maternally inherited coronary heart disease is associated with a novel mitochondrial trna mutation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912950/
https://www.ncbi.nlm.nih.gov/pubmed/31842766
http://dx.doi.org/10.1186/s12872-019-01284-4
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