p62/SQSTM1 droplets initiate autophagosome biogenesis and oxidative stress control

Abstract

Selective autophagy contributes to the degradation of condensates, such as sequestosome 1-bodies, also called p62/SQSTM1-bodies. We showed that endogenous p62 forms gel-like structures, which serve as platforms for autophagosome formation and nuclear factor erythroid 2-related factor 2 (NRF2) activation. Further, p62-mediated NRF2 activation is not cytotoxic, but combination of NRF2 activation with impaired bulk and selective autophagy causes liver injury.

Keywords

• p62/sqstm1
• liquid-liquid phase separation
• autophagy
• oxidative stress
• lc3
• gabarap
• nrf2
• keap1