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. Epub 2022 Mar 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagosomes* / metabolism
  • Autophagy
  • Dyneins / metabolism
  • Lysosomes* / metabolism
  • Protein Transport

Substances

  • Dyneins