1. Academic Validation
  2. Recycling of autophagosomal components from autolysosomes by the recycler complex

Recycling of autophagosomal components from autolysosomes by the recycler complex

  • Nat Cell Biol. 2022 Apr;24(4):497-512. doi: 10.1038/s41556-022-00861-8.
Chuchu Zhou  # 1 Zhe Wu  # 1 Wanqing Du  # 2 Huilin Que 1 Yufen Wang 1 Qinqin Ouyang 3 Fenglei Jian 1 Weigang Yuan 1 Yuan Zhao 1 Rui Tian 1 Ying Li 2 Yang Chen 4 5 Shuaixin Gao 4 5 Catherine C L Wong 4 5 Yueguang Rong 6 7
Affiliations

Affiliations

  • 1 School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • 3 College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China.
  • 4 Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Peking University, Beijing, China.
  • 5 School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing, China.
  • 6 School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 7 Cell Architecture Research Center, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • # Contributed equally.
Abstract

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.

Figures
Products