p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response

: Kageyama Shun, Gudmundsson Sigurdur Runar, Sou Yu-Shin, Ichimura Yoshinobu, Tamura Naoki, Kazuno Saiko, Ueno Takashi, Miura Yoshiki, Noshiro Daisuke, Abe Manabu, Mizushima Tsunehiro, Miura Nobuaki, Okuda Shujiro, Motohashi Hozumi, Lee Jin-A, Sakimura Kenji, Ohe Tomoyuki, Noda Nobuo N, Waguri Satoshi, Eskelinen Eeva-Liisa Komatsu Masaaki

Publisher: SpringerNature

: 2021

: Nature Communications

: Nature communications

: Nat Commun

: 16

: 12

: 1

: 2041-1723

DOI: https://doi.org/10.1038/s41467-020-20185-1

: https://research.utu.fi/converis/portal/Publication/51245853

Autophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress.

s41467-020-20185-1.pdf