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GLUT10 maintains the integrity of major arteries through regulation of redox homeostasis and mitochondrial function

Human Molecular Genetics, ddx401

https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddx401/4630345

Glucose transporter 10 (GLUT10) is a member of the GLUT family of membrane transporters, and mutations in this gene cause arterial tortuosity syndrome (ATS). However, the physiological role and regulation of GLUT10 in arteries remains unclear. To further understand its physiological roles in major arteries, we examined the regulatory mechanisms of GLUT10 in ASMCs and aortic tissues. Interestingly, we find that targeting of GLUT10 to mitochondria is increased in ASMCs under both stress and aging conditions, which enhances dehydroascorbic acid (DHA) uptake and maintains intracellular ascorbic acid (AA) levels. We further demonstrate that the targeting of GLUT10 to mitochondria is important to maintain redox homeostasis, mitochondrial structure and mitochondrial function in ASMCs. A missense mutation of GLUT10 (Glut10G128E) impairs mitochondrial targeting in ASMCs. Consequently, ASMCs isolated from Glut10G128E mice exhibit increased reactive oxygen species (ROS) levels, fragmented mitochondria and impaired mitochondrial function, as well as enhanced cell proliferation and migration. In vivo, mitochondrial structure is altered, and ROS levels are heightened in aortic tissues of Glut10G128E mice. Furthermore, increased number and disorganization of ASMCs, along with progressive arterial wall remodeling were observed in aortic tissues of Glut10G128E mice. These defects were coincident with elevated systolic blood pressure in aged Glut10G128E animals. Our results describe a novel mechanism that GLUT10 targeting to mitochondria under stress and aging condition has a critical role in maintaining AA levels, redox homeostasis and mitochondrial structure and function in ASMCs, which is likely to contribute to the maintenance of healthy vascular tissue.
 

 


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115台北市南港區研究院路二段128號
Tel: 02-27899515
Fax: 02-27858059
icob@gate.sinica.edu.tw
Copyright © ICOB 2013. All rights reserved. 最佳瀏覽網頁方式請用最新版IE11或其他瀏覽器 /瀏覽人數:1312615--
 瀏覽人數:1312615