The landscape of mitophagy in sepsis reveals PHB1 as an NLRP3 inflammasome inhibitor

• DOI: 10.3389/fimmu.2023.1188482
• Publication Date: 2023-06-08T04:57:30Z
• Authors: Shipeng Chen; Jinqi Ma; Ping Yin; Fang Liang
• Keywords: Inflammasomes; Immunology; PHB1; Mitophagy; RC581-607; immunity; NLRP3 inflammasome; 3. Good health; sepsis; mitophagy; Sepsis; NLR Family, Pyrin Domain-Containing 3 Protein; Humans; Immunologic diseases. Allergy

Mitophagy is a selective autophagy targeting damaged and potential cytotoxic mitochondria, which can effectively prevent excessive production from mitochondria alleviate the inflammatory response. However, role of mitophagy in sepsis remains poorly explored. Here, we studied its immune heterogeneity. By performing mitophagy-related typing on 348 samples, three clusters (A, B, C) were obtained. Cluster A had highest degree accompanied by lowest disease severity, while cluster C with severity. The unique characteristics. We further revealed that expression PHB1 these was significantly different negatively correlated severity sepsis, suggesting involved development sepsis. It has been reported impaired leads to over-activation inflammasomes, promotes development. Further analysis showed expressions NLRP3 inflammasomes core genes up-regulated PHB1. Next, verified whether downregulation caused activation found knockdown increased levels mtDNA cytoplasm enhanced inflammasomes. In addition, inhibitor treatment abolished knockdown-mediated inhibited through mitophagy. conclusion, this study reveals high may predict good outcome key inflammasome regulator