Mitochondrial DNA synthesis fuels NLRP3 inflammasome

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2018,（11）
• 页码范围: 1046-1047
• 页数: 2页
• 语种: 英文

摘要

Mitochondria-derived signals are associated with NLRP3 inflammasome activation.A recent study in Nature by Zhong et al.shows that inflammasome priming drives new mitochondrial DNA synthesis,and proposes this to be a prerequisite for NLRP3 inflammasome signaling. NLRP3 is a cytosolic pattern recognition receptor that is activated in response to a broad range of pathogen-derived and endogenous agents.NLRP3 assembles an inflammasome complex with ASC to activate caspase-1,which drives the maturation and secretion of the pro-inflammatory cytokines IL-1β and IL-18,and concurrently induces Gasdermin-D-dependent cell lysis.NLRP3 contributes to many acquired and hereditary inflammatory diseases (e.g.,Alzheimer's,gout,Muckle-Wells syndrome).1 The mechanism of NLRP3 activation is complex,and tightly regulated by processes broadly categorized into two stages.Signal one,the "priming" or "licensing" signal,serves two functions:it enhances expression of NLRP3 and pro-IL-1β,and triggers NLRP3 posttranslational modifications.Signal two then triggers NLRP3 activation via pathways involving potassium efflux and/or mitochondria,1 resulting in inflammasome assembly and signaling.