論文 - 詳細
| RRC ID | 69009 |
|---|---|
| 著者 | Kurane T, Matsunaga T, Ida T, Sawada K, Nishimura A, Fukui M, Umemura M, Nakayama M, Ohara N, Matsumoto S, Akaike T, Matsuzaki G, Takaesu G. |
| タイトル | GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation. |
| ジャーナル | FASEB J |
| Abstract |
Tuberculosis is a communicable disease caused by Mycobacterium tuberculosis which primarily infects macrophages and establishes intracellular parasitism. A mycobacterial virulence factor Zn2+ 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. |
| 巻・号 | 36(1) |
| ページ | e22096 |
| 公開日 | 2022-1-1 |
| DOI | 10.1096/fj.202101074RR |
| PMID | 34907600 |
| MeSH | Animals Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism* Bacterial Proteins Gene Knockdown Techniques HEK293 Cells Humans Inflammasomes / genetics Inflammasomes / metabolism* Macrophages / metabolism* Metalloproteases Mice Mitochondrial Membranes / metabolism Mycobacterium tuberculosis / genetics Mycobacterium tuberculosis / metabolism* NADH, NADPH Oxidoreductases / genetics NADH, NADPH Oxidoreductases / metabolism* NLR Family, Pyrin Domain-Containing 3 Protein / genetics NLR Family, Pyrin Domain-Containing 3 Protein / metabolism* |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | J774.1(RCB0434) |