Zhou Chuchu, Wu Zhe, Du Wanqing, Que Huilin, Wang Yufen, Ouyang Qinqin, Jian Fenglei, Yuan Weigang, Zhao Yuan, Tian Rui, Li Ying, Chen Yang, Gao Shuaixin, Wong Catherine C L, Rong Yueguang
School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Nat Cell Biol. 2022 Apr;24(4):497-512. doi: 10.1038/s41556-022-00861-8. Epub 2022 Mar 24.
Autolysosomes contain components from autophagosomes and lysosomes. The contents inside the autolysosomal lumen are degraded during autophagy, while the fate of autophagosomal components on the autolysosomal membrane remains unknown. Here we report that the autophagosomal membrane components are not degraded, but recycled from autolysosomes through a process coined in this study as autophagosomal components recycling (ACR). We further identified a multiprotein complex composed of SNX4, SNX5 and SNX17 essential for ACR, which we termed 'recycler'. In this, SNX4 and SNX5 form a heterodimer that recognizes autophagosomal membrane proteins and is required for generating membrane curvature on autolysosomes, both via their BAR domains, to mediate the cargo sorting process. SNX17 interacts with both the dynein-dynactin complex and the SNX4-SNX5 dimer to facilitate the retrieval of autophagosomal membrane components. Our discovery of ACR and identification of the recycler reveal an important retrieval and recycling pathway on autolysosomes.
自噬溶酶体包含来自自噬体和溶酶体的成分。自噬溶酶体腔内的内容物在自噬过程中被降解，而自噬溶酶体膜上自噬体成分的命运仍不清楚。在此，我们报告自噬体膜成分不会被降解，而是通过本研究中命名为自噬体成分循环（ACR）的过程从自噬溶酶体中回收利用。我们进一步鉴定出一种由SNX4、SNX5和SNX17组成的多蛋白复合物，它对ACR至关重要，我们将其称为“回收器”。其中，SNX4和SNX5形成异源二聚体，识别自噬体膜蛋白，并且通过其BAR结构域在自噬溶酶体上产生膜曲率，以介导货物分选过程。SNX17与动力蛋白-动力蛋白激活蛋白复合物以及SNX4-SNX5二聚体相互作用，以促进自噬体膜成分的回收。我们对ACR的发现以及对回收器的鉴定揭示了自噬溶酶体上一条重要的回收利用途径。
