Zheng Yanrong, Zhang Xiangnan, Chen Zhong
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2017 Jan 25;46(1):92-96. doi: 10.3785/j.issn.1008-9292.2017.02.14.
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.
自噬对于维持细胞内稳态至关重要。作为研究最为深入的选择性自噬之一，线粒体自噬（mitophagy）对于清除受损线粒体至关重要。线粒体自噬功能障碍已被证明与许多人类疾病密切相关。Nix是网织红细胞成熟过程中线粒体自噬的关键蛋白。然而，Nix介导的线粒体自噬的详细分子机制尚未完全阐明。本文总结了Nix在诱导线粒体自噬中的三种可能作用模式。首先，Nix可与线粒体自噬的另一个重要蛋白Parkin相互作用，启动线粒体自噬。其次，Nix可通过其LIR基序与Atg8家族相互作用，作为自噬机制的受体。最后，作为仅含BH3结构域的蛋白，Nix可与Beclin-1竞争，结合Bcl-2家族的其他成员，导致胞质中游离Beclin-1增加，进而促进自噬通量。
