Jan, 2022
GRIM‐19 is a target of mycobacterial Zn 2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation
The FASEB Journal
- Volume
- 36
- Number
- 1
- First page
- e22096
- Last page
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1096/fj.202101074rr
- Publisher
- Wiley
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.
- Link information
-
- DOI
- https://doi.org/10.1096/fj.202101074rr
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/34907600
- URL
- https://onlinelibrary.wiley.com/doi/pdf/10.1096/fj.202101074RR
- URL
- https://onlinelibrary.wiley.com/doi/full-xml/10.1096/fj.202101074RR
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85122038789&origin=inward Open access
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85122038789&origin=inward
- ID information
-
- DOI : 10.1096/fj.202101074rr
- ISSN : 0892-6638
- eISSN : 1530-6860
- Pubmed ID : 34907600
- SCOPUS ID : 85122038789