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The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes

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Rodrigue-Gervais, Ian Gaël; Doiron, Karine; Champagne, Claudia; Mayes, Lindsey; Leiva-Torres, Gabriel A.; Vanié, Paulin JR; Douglas, Todd; Vidal, Silvia M; Alnemri, Emad S.; Saleh, Maya (2018). The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes Scientific Reports , vol. 8 , nº 1: 8446. p. 1-11. DOI: 10.1038/s41598-018-26603-1.

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Résumé

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.

Type de document: Article
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 04 mars 2019 18:50
Dernière modification: 04 mars 2019 18:50
URI: http://espace.inrs.ca/id/eprint/7482

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