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Prominin样蛋白是CD133的同源物,与ND20相互作用以维持线粒体功能。

Prominin-like, a homolog of CD133, interacts with ND20 to maintain mitochondrial function.

作者信息

Wang Xuexiang, Zheng Huimei, Jia Zexiao, Lei Zhaoying, Li Mengyao, Zhuang Qianqian, Zhou Hui, Qiu Yue, Fu Yong, Yang Xiaohang, Xi Yongmei, Yan Qingfeng

机构信息

1College of Life Science, Zhejiang University, Hangzhou, 310058 Zhejiang China.

2Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, 250000 Shandong China.

出版信息

Cell Biosci. 2019 Dec 19;9:101. doi: 10.1186/s13578-019-0365-0. eCollection 2019.

Abstract

BACKGROUND

Prominin-like is a homolog of mammalian CD133, which is recognized as a biomarker for stem cells. The interacting proteins of CD133 and their biological functions remain elusive.

RESULTS

In this study, we using yeast two-hybrid assays, GST pull-down assay and co-immunoprecipitation (Co-IP) methods found that Prominin-like interacts with ND20, a subunit of mitochondrial respiratory complex I. Bioinformatics analysis suggests that Prominin-like is a six-transmembrane glycoprotein which localizes on cellular membranes. Immunostaining and mitochondrial fractionation indicate that Prominin-like could localize in the mitochondria. The knockdown of - in S2 cells resulted in transient mitochondrial dysfunctions as evidenced by reduced ATP production, elevated ROS generation and an accompanied reduction in mitochondrial proteins. Mitochondrial dysfunctions were detected in aged - mutant flies.

CONCLUSION

Our data indicates that Prominin-like acts to maintain mitochondrial function through its interaction with ND20 which, itself, is active in the mitochondrial electron transport chain. Our study provides insights into a novel molecular mechanism of - and suggests a similar function of CD133 in mammals.

摘要

背景

类Prominin是哺乳动物CD133的同源物,CD133被认为是干细胞的生物标志物。CD133的相互作用蛋白及其生物学功能仍不清楚。

结果

在本研究中,我们使用酵母双杂交试验、GST下拉试验和免疫共沉淀(Co-IP)方法发现类Prominin与线粒体呼吸复合物I的一个亚基ND20相互作用。生物信息学分析表明类Prominin是一种定位于细胞膜的六跨膜糖蛋白。免疫染色和线粒体分级分离表明类Prominin可定位于线粒体。在S2细胞中敲低导致短暂的线粒体功能障碍,表现为ATP生成减少、ROS生成增加以及线粒体蛋白随之减少。在老年突变果蝇中检测到线粒体功能障碍。

结论

我们的数据表明类Prominin通过与ND20相互作用来维持线粒体功能,而ND20本身在线粒体电子传递链中具有活性。我们的研究为……提供了一种新的分子机制见解,并提示CD133在哺乳动物中具有类似功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c342/6923988/de9d03a7784d/13578_2019_365_Fig1_HTML.jpg

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