ORCID

Abstract

SQSTM1/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.

DOI

10.1080/15548627.2024.2340413

Publication Date

2024-01-01

Publication Title

Autophagy

Volume

20

Issue

9

ISSN

1554-8627

Keywords

Autophagy, NLRP3 inflammasome, P-bodies, PYCARD, SQSTM1, Sequestosome-1 Protein/metabolism, Animals, Inflammasomes/metabolism, Autophagy/physiology, Humans, Mice, DEAD-box RNA Helicases/metabolism

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

First Page

2100

Last Page

2101

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