Integrated proteomics identifies p62-dependent selective autophagy of the supramolecular vault complex

Reo Kurusu, Yuki 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

研究成果: ジャーナルへの寄稿学術誌査読

10 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1189-1205.e11
ジャーナルDevelopmental Cell
58
13
DOI
出版ステータス出版済み - 7月 10 2023
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 生化学、遺伝学、分子生物学一般
  • 発生生物学
  • 細胞生物学

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