p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response
Miura Nobuaki; Noshiro Daisuke; Mizushima Tsunehiro; Kageyama Shun; Lee Jin-A; Ohe Tomoyuki; Abe Manabu; Motohashi Hozumi; Miura Yoshiki; Okuda Shujiro; Sakimura Kenji; Noda Nobuo N; Kazuno Saiko; Tamura Naoki; Ueno Takashi; Eskelinen Eeva-Liisa Komatsu Masaaki; Ichimura Yoshinobu; Waguri Satoshi; Gudmundsson Sigurdur Runar; Sou Yu-Shin
p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response
Miura Nobuaki
Noshiro Daisuke
Mizushima Tsunehiro
Kageyama Shun
Lee Jin-A
Ohe Tomoyuki
Abe Manabu
Motohashi Hozumi
Miura Yoshiki
Okuda Shujiro
Sakimura Kenji
Noda Nobuo N
Kazuno Saiko
Tamura Naoki
Ueno Takashi
Eskelinen Eeva-Liisa Komatsu Masaaki
Ichimura Yoshinobu
Waguri Satoshi
Gudmundsson Sigurdur Runar
Sou Yu-Shin
SpringerNature
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042826334
https://urn.fi/URN:NBN:fi-fe2021042826334
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]