A new role of the early endosome in restricting NLRP3 inflammasome via mitophagy. Issue 6 (3rd June 2022)

• Record Type: Journal Article
• Authors: Wu, Kelvin Ka Lok; Cheng, Kenneth King Yip
• Is Part Of: Autophagy. Volume 18:Issue 6(2022)
• Page Start: 1475
• Page End: 1477
• Publication Date: 2022-06-03
• Subjects: APPL1 -- early endosome -- mitochondria -- mitophagy -- NLRP3 inflammasome -- RAB5; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2022.2040314
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: NLRP3 (NLR family pyrin domain containing 3) inflammasome is a potent mediator of inflammation due to its ability to produce the pro-inflammatory cytokines IL1B (interleukin 1 beta) and IL18 in response to numerous danger signals and pathogens. Mitophagy, a selective form of autophagy, restricts NLRP3 inflammasome activation by limiting the mitochondrial-derived danger signals. Here, we demonstrated that the adaptor protein APPL1 together with its interaction partner RAB5 in early endosomes negatively regulate NLRP3 inflammasome activation via induction of mitophagy in macrophages. Hematopoietic-deletion of Appl1 exacerbates systemic NLRP3 inflammasome activation in rodent models under obese or septic conditions. Our study identified a new regulatory network between early endosomes and mitochondria in control of NLRP3 inflammasome activation.