Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes
Authors: Suresh Kumar, Ruheena Javed, Michal Mudd, Sandeep Pallikkuth, Keith A. Lidke, Ashish Jain, Karthikeyan Tangavelou, Sigurdur Runar Gudmundsson, Chunyan Ye, Tor Erik Rusten, Jan Haug Anonsen, Alf Håkon Lystad, Aurore Claude-Taupin, Anne Simonsen, Michelle Salemi, Brett Phinney, Jing Li, Lian-Wang Guo, Steven B. Bradfute, Graham S. Timmins, Eeva-Liisa Eskelinen, Vojo Deretic
Summary:
The biogenesis of mammalian autophagosomes remains to be fully defined. Here, we used cellular and in vitro membrane fusion analyses to show that autophagosomes are formed from a hitherto unappreciated hybrid membrane compartment. The autophagic precursors emerge through fusion of FIP200 vesicles, derived from the cis-Golgi, with endosomally derived ATG16L1 membranes to generate a hybrid pre-autophagosomal structure, HyPAS. A previously unrecognized apparatus defined here controls HyPAS biogenesis and mammalian autophagosomal precursor membranes. HyPAS can be modulated by pharmacological agents whereas its formation is inhibited upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or by expression of SARS-CoV-2 nsp6. These findings reveal the origin of mammalian autophagosomal membranes, which emerge via convergence of secretory and endosomal pathways, and show that this process is targeted by microbial factors such as coronaviral membrane-modulating proteins.
Source: Cell, 2021; 184 (24): 5950
Summary:
The biogenesis of mammalian autophagosomes remains to be fully defined. Here, we used cellular and in vitro membrane fusion analyses to show that autophagosomes are formed from a hitherto unappreciated hybrid membrane compartment. The autophagic precursors emerge through fusion of FIP200 vesicles, derived from the cis-Golgi, with endosomally derived ATG16L1 membranes to generate a hybrid pre-autophagosomal structure, HyPAS. A previously unrecognized apparatus defined here controls HyPAS biogenesis and mammalian autophagosomal precursor membranes. HyPAS can be modulated by pharmacological agents whereas its formation is inhibited upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or by expression of SARS-CoV-2 nsp6. These findings reveal the origin of mammalian autophagosomal membranes, which emerge via convergence of secretory and endosomal pathways, and show that this process is targeted by microbial factors such as coronaviral membrane-modulating proteins.
Source: Cell, 2021; 184 (24): 5950