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Sestrin2 acts as a negative regulator of inflammasome activation by inducing mitophagy
DC Field | Value | Language |
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dc.contributor.author | 김민지 | - |
dc.date.accessioned | 2017-01-26T05:40:05Z | - |
dc.date.available | 2017-01-26T05:40:05Z | - |
dc.date.issued | 2015 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/145562 | - |
dc.description | Dept. of Medical Science/박사 | - |
dc.description.abstract | In “danger” conditions, such as infections, the NLRP3 inflammasome complex is positively regulated by mitochondria-generated reactive oxygen species and negatively regulated by autophagy. Thus, tight regulation of both mitochondrial integrity and autophagy is essential for proper inflammasome activation. Here, I demonstrate that Sestrin2 suppressed continuous inflammasome activation by preserving mitochondrial homeostasis through inducing selective autophagy. Sestrin2 plays a dual role to remove damaged mitochondria caused by stimulation with LPS and ATP in macrophages. First, Sestrin2 facilitates the perinuclear clustering of damaged mitochondria by mediating aggregation of p62/SQSTM1 and its recruitment to Lys 63 ubiquitins on mitochondria surface. Second, Sestrin2 induces autophagosome formation and mitophagy through maintenance of ULK1 stability. Thus, both Sestrin2- and p62-deficient mice had more damaged mitochondria, and produced more caspase-1-dependent cytokines, including IL-1β and IL-18, and had higher mortality in sepsis models. These findings identify a novel role of Sestrin2 and p62 for protection against incessant inflammation. | - |
dc.description.statementOfResponsibility | open | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Sestrin2 acts as a negative regulator of inflammasome activation by inducing mitophagy | - |
dc.type | Thesis | - |
dc.contributor.alternativeName | Kim, Min Ji | - |
dc.type.local | Dissertation | - |
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