A1 Journal article – refereed

Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes




List of Authors: Kumar S, Javed R, Mudd M, Pallikkuth S, Lidke KA, Jain A, Tangavelou K, Gudmundsson SR, Ye CY, Rusten TE, Anonsen JH, Lystad AH, Claude-Taupin A, Simonsen A, Salemi M, Phinney B, Li J, Guo LW, Bradfute SB, Timmins GS, Eskelinen EL, Deretic V

Publisher: CELL PRESS

Publication year: 2021

Journal: Cell

Journal name in source: CELL

Journal acronym: CELL

Volume number: 184

Issue number: 24

Number of pages: 43

ISSN: 0092-8674

DOI: http://dx.doi.org/10.1016/j.cell.2021.10.017


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 (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.


Last updated on 2021-09-12 at 09:47