复印件
内质网
细胞生物学
生物
高尔基体
自噬
膜泡运输蛋白质类
ATP酶
溶酶体
突变体
生物化学
酶
分泌途径
内体
细胞凋亡
液泡蛋白分选
基因
细胞内
作者
Yiwei Sun,Xi Wang,Xiaotong Yang,Lei Wang,Jingjin Ding,Chih-chen Wang,Hong Zhang,Xi Wang
标识
DOI:10.1016/j.devcel.2023.10.007
摘要
Endoplasmic reticulum (ER)-phagy is crucial to regulate the function and homeostasis of the ER via lysosomal degradation, but how it is initiated is unclear. Here we discover that Z-AAT, a disease-causing mutant of α1-antitrypsin, induces noncanonical ER-phagy at ER exit sites (ERESs). Accumulation of misfolded Z-AAT at the ERESs impairs coat protein complex II (COPII)-mediated ER-to-Golgi transport and retains V0 subunits that further assemble V-ATPase at the arrested ERESs. V-ATPase subsequently recruits ATG16L1 onto ERESs to mediate in situ lipidation of LC3C. FAM134B-II is then recruited by LC3C via its LIR motif and elicits ER-phagy leading to efficient lysosomal degradation of Z-AAT. Activation of this ER-phagy mediated by the V-ATPase-ATG16L1-LC3C axis (EVAC) is also triggered by blocking ER export. Our findings identify a pathway which switches COPII-mediated transport to lysosomal degradation for ER quality control.
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