Cargando…
Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility
Vascular smooth muscle cell (SMC) from arterial stenotic-occlusive diseases is featured with deficiency in mitochondrial respiration and loss of cell contractility. However, the regulatory mechanism of mitochondrial genes and mitochondrial energy metabolism in SMC remains elusive. Here, we described...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971246/ https://www.ncbi.nlm.nih.gov/pubmed/31959742 http://dx.doi.org/10.1038/s41419-020-2240-7 |
_version_ | 1783489683937820672 |
---|---|
author | Liu, Yue-Feng Zhu, Juan-Juan Yu Tian, Xiao Liu, Han Zhang, Tao Zhang, Yun-Peng Xie, Si-An Zheng, Ming Kong, Wei Yao, Wei-Juan Pang, Wei Zhao, Chuan-Rong Tang, Yuan-Jun Zhou, Jing |
author_facet | Liu, Yue-Feng Zhu, Juan-Juan Yu Tian, Xiao Liu, Han Zhang, Tao Zhang, Yun-Peng Xie, Si-An Zheng, Ming Kong, Wei Yao, Wei-Juan Pang, Wei Zhao, Chuan-Rong Tang, Yuan-Jun Zhou, Jing |
author_sort | Liu, Yue-Feng |
collection | PubMed |
description | Vascular smooth muscle cell (SMC) from arterial stenotic-occlusive diseases is featured with deficiency in mitochondrial respiration and loss of cell contractility. However, the regulatory mechanism of mitochondrial genes and mitochondrial energy metabolism in SMC remains elusive. Here, we described that DNA methyltransferase 1 (DNMT1) translocated to the mitochondria and catalyzed D-loop methylation of mitochondrial DNA in vascular SMCs in response to platelet-derived growth factor-BB (PDGF-BB). Mitochondrial-specific expression of DNMT1 repressed mitochondrial gene expression, caused functional damage, and reduced SMC contractility. Hypermethylation of mitochondrial D-loop regions were detected in the intima-media layer of mouse carotid arteries subjected to either cessation of blood flow or mechanical endothelial injury, and also in vessel specimens from patients with carotid occlusive diseases. Likewise, the ligated mouse arteries exhibited an enhanced mitochondrial binding of DNMT1, repressed mitochondrial gene expression, defects in mitochondrial respiration, and impaired contractility. The impaired contractility of a ligated vessel could be restored by ex vivo transplantation of DNMT1-deleted mitochondria. In summary, we discovered the function of DNMT1-mediated mitochondrial D-loop methylation in the regulation of mitochondrial gene transcription. Methylation of mitochondrial D-loop in vascular SMCs contributes to impaired mitochondrial function and loss of contractile phenotype in vascular occlusive disease. |
format | Online Article Text |
id | pubmed-6971246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69712462020-01-22 Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility Liu, Yue-Feng Zhu, Juan-Juan Yu Tian, Xiao Liu, Han Zhang, Tao Zhang, Yun-Peng Xie, Si-An Zheng, Ming Kong, Wei Yao, Wei-Juan Pang, Wei Zhao, Chuan-Rong Tang, Yuan-Jun Zhou, Jing Cell Death Dis Article Vascular smooth muscle cell (SMC) from arterial stenotic-occlusive diseases is featured with deficiency in mitochondrial respiration and loss of cell contractility. However, the regulatory mechanism of mitochondrial genes and mitochondrial energy metabolism in SMC remains elusive. Here, we described that DNA methyltransferase 1 (DNMT1) translocated to the mitochondria and catalyzed D-loop methylation of mitochondrial DNA in vascular SMCs in response to platelet-derived growth factor-BB (PDGF-BB). Mitochondrial-specific expression of DNMT1 repressed mitochondrial gene expression, caused functional damage, and reduced SMC contractility. Hypermethylation of mitochondrial D-loop regions were detected in the intima-media layer of mouse carotid arteries subjected to either cessation of blood flow or mechanical endothelial injury, and also in vessel specimens from patients with carotid occlusive diseases. Likewise, the ligated mouse arteries exhibited an enhanced mitochondrial binding of DNMT1, repressed mitochondrial gene expression, defects in mitochondrial respiration, and impaired contractility. The impaired contractility of a ligated vessel could be restored by ex vivo transplantation of DNMT1-deleted mitochondria. In summary, we discovered the function of DNMT1-mediated mitochondrial D-loop methylation in the regulation of mitochondrial gene transcription. Methylation of mitochondrial D-loop in vascular SMCs contributes to impaired mitochondrial function and loss of contractile phenotype in vascular occlusive disease. Nature Publishing Group UK 2020-01-20 /pmc/articles/PMC6971246/ /pubmed/31959742 http://dx.doi.org/10.1038/s41419-020-2240-7 Text en © The Author(s) 2020 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, Yue-Feng Zhu, Juan-Juan Yu Tian, Xiao Liu, Han Zhang, Tao Zhang, Yun-Peng Xie, Si-An Zheng, Ming Kong, Wei Yao, Wei-Juan Pang, Wei Zhao, Chuan-Rong Tang, Yuan-Jun Zhou, Jing Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility |
title | Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility |
title_full | Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility |
title_fullStr | Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility |
title_full_unstemmed | Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility |
title_short | Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility |
title_sort | hypermethylation of mitochondrial dna in vascular smooth muscle cells impairs cell contractility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971246/ https://www.ncbi.nlm.nih.gov/pubmed/31959742 http://dx.doi.org/10.1038/s41419-020-2240-7 |
work_keys_str_mv | AT liuyuefeng hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT zhujuanjuan hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT yutianxiao hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT liuhan hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT zhangtao hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT zhangyunpeng hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT xiesian hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT zhengming hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT kongwei hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT yaoweijuan hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT pangwei hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT zhaochuanrong hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT tangyuanjun hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility AT zhoujing hypermethylationofmitochondrialdnainvascularsmoothmusclecellsimpairscellcontractility |