Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes.

Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes.
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DOI:
10.1016/j.cell.2021.10.017
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发表时间:
2021-11-24
期刊:
影响因子:
64.5
通讯作者:
Deretic V
Deretic V
中科院分区:
生物学1区
文献类型:
--
作者:
Kumar S;Javed R;Mudd M;Pallikkuth S;Lidke KA;Jain A;Tangavelou K;Gudmundsson SR;Ye C;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

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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 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. Insights into the origin of mammalian autophagosomal membrane and its inhibition by SARS-CoV-2
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