ASC deglutathionylation is a checkpoint for NLRP3 inflammasome activation
| العنوان: | ASC deglutathionylation is a checkpoint for NLRP3 inflammasome activation |
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| المؤلفون: | Shuhang Li, Jiwei Liu, Zhihao Xu, Tengchuan Jin, Rufeng Xue, Rongbin Zhou, Yuanyuan Huang, Shiyu Bai, Jizhong Lou, Junjie Hou, Tao Xu, Li Bai, Linfeng Xu, Fanwu Gong, Linlin Wang, Qielan Wu, Xiaofei Yang, Bolong Lin, Pingyong Xu, Ting Yue, Huimin Zhang, Yanhong Xue |
| المصدر: | Journal of Experimental Medicine. 218 |
| بيانات النشر: | Rockefeller University Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Mitochondrial ROS, endocrine system, Cell cycle checkpoint, Inflammasomes, animal diseases, Immunology, Mutant, Endoplasmic Reticulum, In vivo, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Immunology and Allergy, Triglycerides, Glutathione Transferase, integumentary system, Chemistry, Macrophages, hemic and immune systems, Inflammasome, Mice, Mutant Strains, eye diseases, Cell biology, CARD Signaling Adaptor Proteins, Mice, Inbred C57BL, NLRP3 inflammasome activation, Carrier Proteins, Reactive Oxygen Species, medicine.drug |
| الوصف: | Activation of NLRP3 inflammasome is precisely controlled to avoid excessive activation. Although multiple molecules regulating NLRP3 inflammasome activation have been revealed, the checkpoints governing NLRP3 inflammasome activation remain elusive. Here, we show that activation of NLRP3 inflammasome is governed by GSTO1-promoted ASC deglutathionylation in macrophages. Glutathionylation of ASC inhibits ASC oligomerization and thus represses activation of NLRP3 inflammasome in macrophages, unless GSTO1 binds ASC and deglutathionylates ASC at ER, under control of mitochondrial ROS and triacylglyceride synthesis. In macrophages expressing ASCC171A, a mutant ASC without glutathionylation site, activation of NLRP3 inflammasome is GSTO1 independent, ROS independent, and signal 2 less dependent. Moreover, AscC171A mice exhibit NLRP3-dependent hyperinflammation in vivo. Our results demonstrate that glutathionylation of ASC represses NLRP3 inflammasome activation, and GSTO1-promoted ASC deglutathionylation at ER, under metabolic control, is a checkpoint for activating NLRP3 inflammasome. |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df5cad3d83debec4f2cb674e358b2040 https://doi.org/10.1084/jem.20202637 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....df5cad3d83debec4f2cb674e358b2040 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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