A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes
Tekijät: 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
Kustantaja: CELL PRESS
Julkaisuvuosi: 2021
Journal: Cell
Tietokannassa oleva lehden nimi: CELL
Lehden akronyymi: CELL
Vuosikerta: 184
Numero: 24
Aloitussivu: 5950
Lopetussivu: 5969.e22
Sivujen määrä: 43
ISSN: 0092-8674
DOI: https://doi.org/10.1016/j.cell.2021.10.017
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 (SARSCoV-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.
