The impact of post-translational modifications and subcellular localization on NLRP3 inflammasome activation: A systematic review

Abstract

Background: The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is crucial for innate immunity. However, its uncontrolled and dysregulated activation may cause various inflammatory and autoimmune disorders. Therefore, tight regulation of NLRP3 inflammasome is necessary. Numerous post-translational modifications (PTMs) are reported to play a critical role in regulating NLRP3 inflammasome activation, including (de-)phosphorylation, (de-)ubiquitination, (de-)SUMOylation, (de-)palmitoylation, (de-)acetylation, deglutathionylation, ISGylation, S-nitrosylation, and alkylation. In addition, the subcellular localization of NLRP3, involving endoplasmic reticulum (ER), mitochondria, Golgi, endosomes, and the microtubule-organizing center (MTOC), is also closely related to inflammasome assembly and activation.

Aims of review: This review first describes the effects of recently found PTMs on NLRP3 inflammasome activation. Furthermore, the stage at which PTMs occur is elucidated in detail while previous reviews do not distinguish it very clearly. In addition, based on the subcellular distribution of NLRP3, this review proposes a novel spatiotemporal activation of this inflammasome.

Key scientific concepts of review: This review highlights the innovative findings about the effects of PTMs and localization on NLRP3 inflammasome, which enrich the regulatory networks of this inflammasome and offer references for potential clinical translation in the future.

Graphical abstract:

Keywords: Golgi; Microtubule-organizing center; NLRP3; Post-translational modifications.