GRIM-19 is a target of mycobacterial Zn^<2+> metalloprotease 1 and indispensable for NLRP3 inflammasome activation

• Material Type: 博士論文
• ISSN: 0892-6638
• Title: GRIM-19 is a target of mycobacterial Zn^<2+> metalloprotease 1 and indispensable for NLRP3 inflammasome activation
• Volume: 36 1
• Author/Editor: 藏根, 友美
• Author Heading: 藏根, 友美
• Publication, Distribution, etc.: 琉球大学
• Publication Date: 2022-03-18
• Publication Date (W3CDTF): 2022-03-18
• Alternative Title: GRIM-19は結核菌のZn^<2+>メタロプロテアーゼの標的であり、NLRP3インフラマソームの活性化に必須である
• Periodical title: FASEB Journal
• Degree grantor/type: 琉球大学
• Date Granted: 2022-03-18
• Date Granted (W3CDTF): 2022-03-18
• Dissertation Number: 甲第541号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲第541号
• Text Language Code: eng
• Alias of Author: Kurane, Tomomi
• Subject Heading: inflammasome; interleukin-1β; macrophages; mitochondria; Mycobacterium tuberculosis
• Target Audience: 一般
• Note (General): Tuberculosis is a communicable disease caused by Mycobacterium tuberculosis which primarily infects macrophages and establishes intracellular parasitism. A mycobacterial virulence factor Zn^<2+> metalloprotease 1 (Zmp1) is known to suppress interleukin (IL)-1β production by inhibiting caspase-1 resulting in phagosome maturation arrest. However, the molecular mechanism of caspase-1 inhibition by Zmp1 is still elusive. Here, we identified GRIM-19 (also known as NDUFA13), an essential subunit of mitochondrial respiratory chain complex I, as a novel Zmp1-binding protein. Using the CRISPR/Cas9 system, we generated GRIM-19 knockout murine macrophage cell line J774.1 and found that GRIM-19 is essential for IL-1β production during mycobacterial infection as well as in response to NLRP3 inflammasome-activating stimuli such as extracellular ATP or nigericin. We also found that GRIM-19 is required for the generation of mitochondrial reactive oxygen species and NLRP3-dependent activation of caspase-1. Loss of GRIM-19 or forced expression of Zmp1 resulted in a decrease in mitochondrial membrane potential. Our study revealed a previously unrecognized role of GRIM-19 as an essential regulator of NLRP3 inflammasome and a molecular mechanism underlying Zmp1-mediated suppression of IL-1β production during mycobacterial infection.
• Persistent ID (NDL): info:ndljp/pid/12314032; https://dl.ndl.go.jp/pid/12314032
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2022-08-08T06:02:54+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/20.500.12000/0002018035; https://u-ryukyu.repo.nii.ac.jp/records/2018035
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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