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The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1β Activation

Vince, James E; De Nardo, Dominic; Gao, Wenqing; Vince, Angelina J.; Hall, Cathrine; McArthur, Kate; Simpson, Daniel; Vijayaraj, Swarna; Lindqvist, Lisa M.; Bouillet, Philippe; Rizzacasa, Mark A.; Man, Si Ming; Silke, John; Masters, Seth; Lessene, Guillaume; Huang, David C.S.; Gray, Daniel H.D.; Kile, B.T.; Shao, Feng; Lawlor, Kate E.


Intrinsic apoptosis resulting from BAX/BAK-mediated mitochondrial membrane damage is regarded as immunologically silent. We show here that in macrophages, BAX/BAK activation results in inhibitor of apoptosis (IAP) protein degradation to promote caspase-8-mediated activation of IL-1β. Furthermore, BAX/BAK signaling induces a parallel pathway to NLRP3 inflammasome-mediated caspase-1-dependent IL-1β maturation that requires potassium efflux. Remarkably, following BAX/BAK activation, the apoptotic...[Show more]

CollectionsANU Research Publications
Date published: 2018
Type: Journal article
Source: Cell Reports
DOI: 10.1016/j.celrep.2018.10.103
Access Rights: Open Access


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