A1 Journal article – refereed

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




List of Authors: Kageyama S, Gudmundsson SR, Sou YS, Ichimura Y, Tamura N, Kazuno S, Ueno T, Miura Y, Noshiro D, Abe M, Mizushima T, Miura N, Okuda S, Motohashi H, Lee JA, Ohe T, Sakimura K, Waguri S, Noda NN, Komatsu M, Eskelinen EL

Publication year: 2021

Journal: Nature Communications

Journal name in source: Nature communications

Journal acronym: Nat Commun

Volume number: 12

Issue number: 1

ISSN: 2041-1723

eISSN: 2041-1723

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


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 2021-24-06 at 09:00