Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M112.340315
Title: Function of GRIM-19, a mitochondrial respiratory chain complex I protein, in innate immunity
Authors: Chen, Y.
Lu, H.
Liu, Q.
Huang, G.
Lim, C.P. 
Zhang, L.
Hao, A.
Cao, X.
Issue Date: 3-Aug-2012
Citation: Chen, Y., Lu, H., Liu, Q., Huang, G., Lim, C.P., Zhang, L., Hao, A., Cao, X. (2012-08-03). Function of GRIM-19, a mitochondrial respiratory chain complex I protein, in innate immunity. Journal of Biological Chemistry 287 (32) : 27227-27235. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M112.340315
Abstract: Mitochondria respiratory chain (RC), consisting of five multisubunit complexes, is crucial for cellular energy production, reactive oxygen species generation, and regulation of apoptosis. Recently, a few mitochondrial proteins have been reported to be essential for innate immunity, but the function of mitochondrial RC in innate immunity is largely unknown. By knock-out of GRIM-19, a newly identified subunit protein of mitochondrial complex I, in mice, we found that heterogeneous mice (GRIM-19+/-) are prone to spontaneous urinary tract infection, mostly by Staphylococcus saprophyticus. Macrophages derived from these mice have compromised mitochondrial complex I activity and increased reactive oxygen species level. Bacterial infection induces a rapid up-regulation of GRIM-19 and complex I activity in the wild-type macrophages, but both are reduced in the macrophages from GRIM-19+/- mice. These cells also have decreased intracellular killing ability against S. saprophyticus. The defects for this probably occur in the fusion of bacteria to lysosome, but not in the bacterial engulfment and macrophage migration. In addition, production of proinflammatory cytokines, such as interleukin (IL)-1, IL-12, IL-6, and interferon (IFN)-γ, induced by both bacterial infection and lipopolysaccharide (LPS) and monodansylcadaverine treatment, is also decreased in the GRIM19+/- macrophages. Inhibition of mitochondrial RC activity by inhibitors shows a similar reduction on the cytokine production. Due to low cytokine production, the inflammatory response caused by in vivo bacterial challenge in the bladders of GRIM-19+/- mice is compromised. This study provides genetic evidence for a critical role of mitochondrial RC in innate immunity. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/111892
ISSN: 00219258
DOI: 10.1074/jbc.M112.340315
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

28
checked on Dec 14, 2019

WEB OF SCIENCETM
Citations

27
checked on Dec 6, 2019

Page view(s)

73
checked on Dec 13, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.