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.
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。