小柯机器人

美国新墨西哥大学Vojo Deretic研究团队发现，哺乳动物的杂交前自噬体结构HyPAS产生自噬体。2021年11月5日，《细胞》杂志在线发表了这项成果。

研究人员用细胞和体外膜融合分析表明，自噬体是由一个迄今未被重视的杂交膜室形成的。自噬前体是通过FIP200小泡的融合而出现的，FIP200小泡来自顺面高尔基体，与来自内体的ATG16L1膜融合，产生一个杂交的前自噬体结构，即HyPAS。如此一个以前未知的细胞器控制着HyPAS的生物生成和哺乳动物的自噬体前体膜。HyPAS可以被药物调节，而它的形成在SARS-CoV-2感染或SARS-CoV-2 nsp6的表达中被抑制。

这些发现揭示了哺乳动物自噬体膜的起源，它是通过分泌和内体途径的汇合而出现的，并表明这一过程是由微生物因素如冠状病毒膜调节蛋白所靶向的。

据悉，哺乳动物自噬体的生物发生仍有待充分定义。

附：英文原文

Title: Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes

Author: Suresh Kumar, Ruheena Javed, Michal Mudd, Sandeep Pallikkuth, Keith A. Lidke, Ashish Jain, Karthikeyan Tangavelou, Sigurdur Runar Gudmundsson, Chunyan Ye, Tor Erik Rusten, Jan Haug Anonsen, Alf Hkon Lystad, Aurore Claude-Taupin, Anne Simonsen, Michelle Salemi, Brett Phinney, Jing Li, Lian-Wang Guo, Steven B. Bradfute, Graham S. Timmins, Eeva-Liisa Eskelinen, Vojo Deretic

Issue&Volume: 2021-11-05

Abstract: The biogenesis of mammalian autophagosomes remains to be fully defined. Here, we usedcellular and in vitro membrane fusion analyses to show that autophagosomes are formed from a hitherto unappreciatedhybrid membrane compartment. The autophagic precursors emerge through fusion of FIP200vesicles, derived from the cis-Golgi, with endosomally derived ATG16L1 membranes to generate a hybrid pre-autophagosomalstructure, HyPAS. A previously unrecognized apparatus defined here controls HyPASbiogenesis and mammalian autophagosomal precursor membranes. HyPAS can be modulatedby pharmacological agents whereas its formation is inhibited upon severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2) infection or by expression of SARS-CoV-2 nsp6.These findings reveal the origin of mammalian autophagosomal membranes, which emergevia convergence of secretory and endosomal pathways, and show that this process istargeted by microbial factors such as coronaviral membrane-modulating proteins.

DOI: 10.1016/j.cell.2021.10.017

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01233-2