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浙江大学学报（医学版）
浙江大学学报（医学版）  2017, Vol. 46 Issue (1): 92-96    DOI: 10.3785/j.issn.1008-9292.2017.02.14
综述     
Nix介导的线粒体自噬机制的研究进展
郑艳榕(),张翔南,陈忠()
浙江大学药学院, 浙江 杭州 310058
Research progress on mechanism of Nix-mediated mitophagy
ZHENG Yanrong(),ZHANG Xiangnan,CHEN Zhong()
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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摘要：

线粒体自噬对于维持细胞稳态至关重要。近年的研究发现，Nix是参与介导线粒体自噬的一个重要蛋白，在许多生理、病理过程中扮演了重要的角色。但是，Nix介导线粒体自噬的具体机制尚不清楚，现主要存在以下三种假说：① Nix可能与另一线粒体自噬关键蛋白Parkin相互作用，共同介导线粒体自噬；② Nix作为一种自噬受体蛋白，通过自身的Atg8家族相互作用模体招募Atg8家族成员至损伤线粒体，导致线粒体移除；③ 作为Bcl-2家族成员，Nix可能与参与自噬泡生成的重要蛋白Beclin-1竞争结合Bcl-2或Bcl-XL，导致细胞质中游离的Beclin-1增加，进而诱导自噬发生。本文阐述了Nix介导线粒体自噬的可能机制，为以Nix作为靶点进行相关疾病的治疗策略提供理论依据。
关键词： 线粒体;  自噬;  微管相关蛋白质类;  综述    
Abstract:

Autophagy is fundamental to maintain cellular homeostasis. As one kind of the most well-studied selective autophagy, autophagy of mitochondria (mitophagy) is crucial for the clearance of damaged mitochondria. Mitophagy dysfunction has been proved to be closely associated with many human diseases. Nix is a key protein for mitophagy during the maturation of reticulocytes. However, the detailed molecular mechanisms underlying Nix-mediated mitophagy are not fully understood. This article summarizes three possible working models of Nix in mitophagy induction. Firstly, Nix can interplay with Parkin, another important protein for mitophagy, to initiate mitophagy. Secondly, Nix can serve as a receptor for autophagy machinery by interacting with Atg8 family through its LIR motif. Finally, as a BH3-only protein, Nix can compete with Beclin-1 to bind other members of Bcl-2 family resulting in increased free Beclin-1 in cytosol, which further promotes autophagy flux.
Key words: Mitochondria    Autophagy    Microtubule-associated proteins    Review
收稿日期: 2016-10-02 出版日期: 2017-07-06
CLC:  R329.28  
基金资助: 国家自然科学基金(81273506);国家自然科学基金(81102429)
通讯作者: 陈忠     E-mail: yanrong_zh@zju.edu.cn;chenzhong@zju.edu.cn
作者简介: 郑艳榕 (1992-), 女, 博士研究生, 主要从事缺血性脑卒中的基础研究; E-mail:yanrong_zh@zju.edu.cn|陈忠 (1968-), 男, 博士, 教授, 博士生导师, 主要从事慢性脑病的分子生物学机制及药物新靶点研究; E-mail: chenzhong@zju.edu.cn
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引用本文:

郑艳榕,张翔南,陈忠. Nix介导的线粒体自噬机制的研究进展[J]. 浙江大学学报（医学版）, 2017, 46(1): 92-96.

ZHENG Yanrong,ZHANG Xiangnan,CHEN Zhong. Research progress on mechanism of Nix-mediated mitophagy. J Zhejiang Univ (Med Sci), 2017, 46(1): 92-96.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2017.02.14    或    http://www.zjujournals.com/med/CN/Y2017/V46/I1/92

图1  Nix介导线粒体自噬的四种可能模式 A：Nix可能通过诱导膜电势降低激活PINK1/Parkin通路，介导线粒体自噬，其中，蛋白X表示Parkin的泛素化底物，如Mfn2、VDAC1等；B：Nix作为Parkin的泛素化底物，被Parkin泛素化后特异性被LC3识别，进而介导线粒体自噬；C：Nix直接通过其LIR模体与Atg8家族成员结合，介导线粒体自噬；D：Nix可能与Beclin-1竞争结合Bcl-2，释放Beclin-1，增强自噬流.
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