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Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes.
Kumar, Suresh; Javed, Ruheena; Mudd, Michal; Pallikkuth, Sandeep; Lidke, Keith A; Jain, Ashish; Tangavelou, Karthikeyan; Gudmundsson, Sigurdur Runar; Ye, Chunyan; Rusten, Tor Erik; Anonsen, Jan Haug; Lystad, Alf Håkon; Claude-Taupin, Aurore; Simonsen, Anne; Salemi, Michelle; Phinney, Brett; Li, Jing; Guo, Lian-Wang; Bradfute, Steven B; Timmins, Graham S; Eskelinen, Eeva-Liisa; Deretic, Vojo.
  • Kumar S; Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Javed R; Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Mudd M; Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Pallikkuth S; Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM, USA.
  • Lidke KA; Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM, USA.
  • Jain A; Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Tangavelou K; Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Gudmundsson SR; University of Iceland, Reykjavík, Iceland.
  • Ye C; Center for Global Health, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Rusten TE; Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Anonsen JH; Institute of Biosciences, University of Oslo, Oslo, Norway.
  • Lystad AH; Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Claude-Taupin A; Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Simonsen A; Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Salemi M; Proteomics Core, University of California Davis, Davis, CA, USA.
  • Phinney B; Proteomics Core, University of California Davis, Davis, CA, USA.
  • Li J; Department of Surgery, University of Virginia, Charlottesville, VA, USA.
  • Guo LW; Department of Surgery, University of Virginia, Charlottesville, VA, USA.
  • Bradfute SB; Center for Global Health, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Timmins GS; Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; School of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Eskelinen EL; Institute of Biomedicine, University of Turku, Turku, Finland.
  • Deretic V; Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: vderetic@salud.unm.edu.
Cell ; 184(24): 5950-5969.e22, 2021 11 24.
Article in English | MEDLINE | ID: covidwho-1499701
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Autophagosomes / COVID-19 Limits: Humans Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.10.017

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Autophagosomes / COVID-19 Limits: Humans Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.10.017