自噬
生物
细胞生物学
蛋白质稳态
金库(建筑)
蛋白质组学
蛋白质组
生物化学
细胞凋亡
结构工程
基因
工程类
作者
Reo Kurusu,Yasuyuki Fujimoto,Hideaki Morishita,Daisuke Noshiro,Shuhei Takada,Koji Yamano,Hideaki Tanaka,Ritsuko Arai,Shun Kageyama,Tomoko Funakoshi,Satoko Komatsu-Hirota,Hikari Taka,Saiko Kazuno,Yoshiki Miura,Masato Koike,Toshifumi Wakai,Satoshi Waguri,Nobuo N. Noda,Masaaki Komatsu
标识
DOI:10.1016/j.devcel.2023.04.015
摘要
In addition to membranous organelles, autophagy selectively degrades biomolecular condensates, in particular p62/SQSTM1 bodies, to prevent diseases including cancer. Evidence is growing regarding the mechanisms by which autophagy degrades p62 bodies, but little is known about their constituents. Here, we established a fluorescence-activated-particle-sorting-based purification method for p62 bodies using human cell lines and determined their constituents by mass spectrometry. Combined with mass spectrometry of selective-autophagy-defective mouse tissues, we identified vault, a large supramolecular complex, as a cargo within p62 bodies. Mechanistically, major vault protein directly interacts with NBR1, a p62-interacting protein, to recruit vault into p62 bodies for efficient degradation. This process, named vault-phagy, regulates homeostatic vault levels in vivo, and its impairment may be associated with non-alcoholic-steatohepatitis-derived hepatocellular carcinoma. Our study provides an approach to identifying phase-separation-mediated selective autophagy cargoes, expanding our understanding of the role of phase separation in proteostasis.
科研通智能强力驱动
Strongly Powered by AbleSci AI