Transformation of autophagic SQSTM1 droplets to SQSTM1-dependent P-bodies

Autophagy. 2024 Apr 10:1-2. doi: 10.1080/15548627.2024.2340413. Online ahead of print.ABSTRACTSQSTM1/p62 droplets play crucial roles in droplets-based macroautophagy/autophagy including selective autophagy and bulk autophagy. We observed that under several stress milieus, SQSTM1 droplets entirely colocalize with P-body markers, and these stress-induced SQSTM1 droplets contain mRNAs. We thus determined that under certain stress conditions, autophagic SQSTM1 droplets are converted to a type of enlarged P-bodies, designated SQSTM1/p62-dependent P-bodies (pd-PBs). Stress-enhanced SQSTM1 droplet formation drives the nucleation of pd-PBs through the interaction between SQSTM1 and the RNA-binding protein DDX6. Furthermore, pd-PBs sequester PYCARD, facilitating the assembly of NLRP3 inflammasomes, and in turn induce inflammation-related cytotoxicity. Our study suggests that under stress settings, autophagic SQSTM1 droplets are transformed to pd-PBs, underlining a critical role of SQSTM1 in P-body condensation.PMID:38600662 | DOI:10.1080/15548627.2024.2340413

Source: Autophagy - April 11, 2024 Category: Cytology Authors: Evelina Valionyte Elizabeth R Barrow Chris R Baxter Sharon Herath Shouqing Luo Source Type: research