气候变化领域集成服务门户(CCPortal): Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells

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DOI	10.1073/PNAS.2014029117
	Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells
	Yamamoto K.; Nogimori Y.; Imamura H.; Ando J.
发表日期	2021
ISSN	00278424
起始页码	33660
结束页码	33667
卷号	117 期号:52
英文摘要	Vascular endothelial cells (ECs) sense and respond to hemodynamic shear stress, which is critical for circulatory homeostasis and the pathophysiology of vascular diseases. The mechanisms of shear stress mechanotransduction, however, remain elusive. We previously demonstrated a direct role of mitochondria in the purinergic signaling of shear stress: shear stress increases mitochondrial adenosine triphosphate (ATP) production, triggering ATP release and Ca2+ signaling via EC purinoceptors. Here, we showed that shear stress rapidly decreases cholesterol in the plasma membrane, thereby activating mitochondrial ATP production. Imaging using domain 4 mutant-derived cholesterol biosensors showed that the application of shear stress to cultured ECs markedly decreased cholesterol levels in both the outer and inner plasma membrane bilayers. Flow cytometry showed that the cholesterol levels in the outer bilayer decreased rapidly after the onset of shear stress, reached a minimum (around 60% of the control level) at 10 min, and plateaued thereafter. After the shear stress ceased, the decreased cholesterol levels returned to those seen in the control. A biochemical analysis showed that shear stress caused both the efflux and the internalization of plasma membrane cholesterol. ATP biosensor imaging demonstrated that shear stress significantly increased mitochondrial ATP production. Similarly, the treatment of cells with methyl-β-cyclodextrin (MβCD), a membrane cholesterol-depleting agent, increased mitochondrial ATP production. The addition of cholesterol to cells inhibited the increasing effects of both shear stress and MβCD on mitochondrial ATP production in a dose-dependent manner. These findings indicate that plasma membrane cholesterol dynamics are closely coupled to mitochondrial oxidative phosphorylation in ECs. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	ATP; Cholesterol; Endothelial cells; Mitochondria; Shear stress
语种	英语
scopus关键词	adenosine triphosphatase; cholesterol; methyl beta cyclodextrin; adenosine triphosphate; beta cyclodextrin; beta cyclodextrin derivative; cholesterol; Article; biochemical analysis; cell culture; cell function; cell interaction; cell membrane; cell membrane transport; cholesterol blood level; controlled study; dose response; enzyme activation; enzyme activity; flow cytometry; human; human cell; image analysis; internalization (cell); oxidative phosphorylation; priority journal; shear stress; vascular endothelial cell; aorta; cell membrane; cytology; endocytosis; endothelium cell; genetic procedures; genetics; lung; mechanical stress; metabolism; mitochondrion; mutation; vascularization; Adenosine Triphosphate; Aorta; beta-Cyclodextrins; Biosensing Techniques; Cell Membrane; Cholesterol; Endocytosis; Endothelial Cells; Humans; Lung; Mitochondria; Mutation; Oxidative Phosphorylation; Stress, Mechanical
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179662
作者单位	Laboratory of System Physiology, Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Tokyo, 113-0033, Japan; Pediatrics, Reproductive, Developmental and Aging Sciences, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655, Japan; Laboratory of Functional Biology, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan; Laboratory of Biomedical Engineering, School of Medicine, Dokkyo Medical University, Tochigi, 321-0293, Japan
推荐引用方式 GB/T 7714	Yamamoto K.,Nogimori Y.,Imamura H.,et al. Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells[J],2021,117(52).
APA	Yamamoto K.,Nogimori Y.,Imamura H.,&Ando J..(2021).Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA	Yamamoto K.,et al."Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).