A1 Refereed original research article in a scientific journal

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



Authors: 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

Publication year: 2021

Journal: Nature Communications

Journal name in source: Nature communications

Journal acronym: Nat Commun

Article number: 16

Volume: 12

Issue: 1

ISSN: 2041-1723

eISSN: 2041-1723

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

Self-archived copy’s web address: https://research.utu.fi/converis/portal/Publication/51245853


Abstract
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.

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Last updated on 2024-26-11 at 12:03