Document Type
Article
Publication Date
5-31-2018
Abstract
Activation of the inflammasome pathway is crucial for effective intracellular host defense. The mitochondrial network plays an important role in inflammasome regulation but the mechanisms linking mitochondrial homeostasis to attenuation of inflammasome activation are not fully understood. Here, we report that the Parkinson's disease-associated mitochondrial serine protease HtrA2 restricts the activation of ASC-dependent NLRP3 and AIM2 inflammasomes, in a protease activity-dependent manner. Consistently, disruption of the protease activity of HtrA2 results in exacerbated NLRP3 and AIM2 inflammasome responses in macrophages ex vivo and systemically in vivo. Mechanistically, we show that the HtrA2 protease activity regulates autophagy and controls the magnitude and duration of inflammasome signaling by preventing prolonged accumulation of the inflammasome adaptor ASC. Our findings identify HtrA2 as a non-redundant mitochondrial quality control effector that keeps NLRP3 and AIM2 inflammasomes in check.
Recommended Citation
Rodrigue-Gervais, Ian Gaël; Doiron, Karine; Champagne, Claudia; Mayes, Lindsey; Leiva-Torres, Gabriel André; Vanié, Paulin; Douglas, Todd; Vidal, Silvia M.; Alnemri, Emad S.; and Saleh, Maya, "The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes." (2018). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 135.
https://jdc.jefferson.edu/bmpfp/135
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
29855523
Language
English
Comments
This article has been peer reviewed. It is the author’s final published version in Scientific Reports, Volume 8, Issue 1, December 2018, Article number 8446.
The published version is available at https://doi.org/10.1038/s41598-018-26603-1. Copyright © Rodrigue-Gervais et al.