自噬
生物
蛋白质稳态
细胞生物学
自噬体
内体
泛素
受体
袋3
蛋白质组学
ATG8型
ATG5型
溶酶体
生物化学
基因
细胞内
细胞凋亡
作者
Susanne Zellner,Martina Schifferer,Christian Münz
出处
期刊:Molecular Cell
[Elsevier]
日期:2021-03-18
卷期号:81 (6): 1337-1354.e8
被引量:37
标识
DOI:10.1016/j.molcel.2021.01.009
摘要
Summary
Autophagy deficiency in fed conditions leads to the formation of protein inclusions highlighting the contribution of this lysosomal delivery route to cellular proteostasis. Selective autophagy pathways exist that clear accumulated and aggregated ubiquitinated proteins. Receptors for this type of autophagy (aggrephagy) include p62, NBR1, TOLLIP, and OPTN, which possess LC3-interacting regions and ubiquitin-binding domains (UBDs), thus working as a bridge between LC3/GABARAP proteins and ubiquitinated substrates. However, the identity of aggrephagy substrates and the redundancy of aggrephagy and related UBD-containing receptors remains elusive. Here, we combined proximity labeling and organelle enrichment with quantitative proteomics to systematically map the autophagic degradome targeted by UBD-containing receptors under basal and proteostasis-challenging conditions in human cell lines. We identified various autophagy substrates, some of which were differentially engulfed by autophagosomal and endosomal membranes via p62 and TOLLIP, respectively. Overall, this resource will allow dissection of the proteostasis contribution of autophagy to numerous individual proteins.
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