p62/SQSTM1 droplets initiate autophagosome biogenesis and oxidative stress control

Eeva-Liisa Eskelinen; Shun Kageyama; Masaaki Komatsu

doi:10.1080/23723556.2021.1890990

p62/SQSTM1 droplets initiate autophagosome biogenesis and oxidative stress control

Mol Cell Oncol. 2021 Mar 9;8(2):1890990. doi: 10.1080/23723556.2021.1890990.

Authors

Eeva-Liisa Eskelinen¹, Shun Kageyama², Masaaki Komatsu²

Affiliations

¹ Institute of Biomedicine, University of Turku, Turku, Finland.
² Department of Physiology, Juntendo University Graduate School of Medicine, Tokyo. Japan.

Abstract

Selective autophagy contributes to the degradation of condensates, such as sequestosome 1-bodies, also called p62/SQSTM1-bodies. We showed that endogenous p62 forms gel-like structures, which serve as platforms for autophagosome formation and nuclear factor erythroid 2-related factor 2 (NRF2) activation. Further, p62-mediated NRF2 activation is not cytotoxic, but combination of NRF2 activation with impaired bulk and selective autophagy causes liver injury.

Keywords: GABARAP; KEAP1; LC3; NRF2; autophagy; liquid-liquid phase separation; oxidative stress; p62/SQSTM1.

Grants and funding

S. K. is supported by a Grant-in-Aid for Scientific Research (C) (20K06549). M.K. is supported by a Grant-in-Aid for Scientific Research on Innovative Areas (19H05706), a Grant-in-Aid for Scientific Research (B) (18H02611), the Japan Society for the Promotion of Science (an A3 foresight program), Japan Agency for Medical Research and Development (AMED-CREST) and the Takeda Science Foundation. The work was supported by JSPS KAKENHI Grant Number JP 16H06276 (AdAMS). E.L.E. was supported by the Academy of Finland (grant No 286787) and Magnus Ehrnrooth Foundation.