Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes - UTU Research Portal

A1 Refereed original research article in a scientific journal

Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes

Authors: 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

Publisher: CELL PRESS

Publication year: 2021

Journal: Cell

Journal name in source: CELL

Journal acronym: CELL

Volume: 184

Issue: 24

First page : 5950

Last page: 5969.e22

Number of pages: 43

ISSN: 0092-8674

DOI: https://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.