BNIP3泛素化及其对低氧引起的线粒体自噬的调控作用

项目名称： BNIP3泛素化及其对低氧引起的线粒体自噬的调控作用

项目编号： No.31271211

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 吴丽颖

作者单位： 中国人民解放军军事医学科学院

项目金额： 80万元

中文摘要： 线粒体自噬是近年新发现的能通过特异性降解受损线粒体清除体内过多活性氧的一种细胞自我调节功能。BNIP3是线粒体自噬的标记分子，能特异激活线粒体自噬的发生。目前报道的BNIP3对线粒体自噬的激活作用主要局限于BNIP3蛋白表达上，BNIP3翻译后修饰是否参与对线粒体自噬的调控还不清楚。磷酸化和糖基化是现在仅知的两种BNIP3翻译后修饰形式。我们在低氧实验中检测到BNIP3可以发生泛素化降解。如果被确证这将是BNIP3被发现的第三种翻译后修饰。另外我们还发现，不同低氧条件下线粒体自噬程度不同，我们推测BNIP3泛素化可能参与介导了低氧对线粒体自噬的调节。为阐明这些问题，本项目将从确证BNIP3泛素化入手，深入研究BNIP3泛素化与低氧引起的线粒体自噬的关系，为线粒体自噬研究注入新的内容。

中文关键词： BNIP3；线粒体自噬；泛素化；磷酸化；低氧

英文摘要： Mitophagy is recently found a new self-regulation function of cell in scavenging redundant reactive oxygen species (ROS) through specific degradation of damaged mitochondria. BNIP3 is a mitophagy marker, which can specifically activate mitophagy. However, the present researches focus on the role of expression of BNIP3 in activating mitophagy. It is unknown that the role of posttranslational modification of BNIP3 in regulating mitophagy. According to the reports, phosphorylation and glycosylation are the only two posttranslational modifications of BNIP3 up to now. In our hypoxia experiments, we found that BNIP3 could be degradated by ubiquitination pathway. If this phenomenon is verified, it will be the third posttranslational modification of BNIP3. Additionally, we noticed that different hypoxia caused different mitophagy, and presumed that BNIP3 ubiquitination might mediate the effect of hypoxia on mitophagy. In order to clarify these questions, in this project we will proceed to confirm the BNIP3 ubiquitination, and explore the regulatory role of BNIP3 ubiquitination in hypoxia-induced mitophagy. Through this project, we try to increase the new contents for mitophagy research.

英文关键词： BNIP3；mitophagy；ubiquitination；phosphorylation；hypoxia