PDF(Pubmed)
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 (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.
摘要：
哺乳动物自噬体的生物发生仍有待完全定义。这里,我们使用细胞和体外膜融合分析显示，自噬体是由迄今未被重视的杂合膜区室形成的。自噬前体通过FIP200囊泡的融合出现，来源于顺式高尔基，与内体衍生的ATG16L1膜生成杂合的自噬体前结构，HyPAS.此处定义的先前未识别的装置控制HyPAS生物发生和哺乳动物自噬小体前体膜。HyPAS可以通过药理学试剂调节,而其形成在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染或通过SARS-CoV-2nsp6的表达而被抑制。这些发现揭示了哺乳动物自噬体膜的起源，通过分泌和内体途径的融合出现，并表明该过程是由微生物因素如冠状病毒膜调节蛋白靶向的。
