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

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