The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
The Mitochondrial Antiviral Protein MAVS Associates with NLRP3 and Regulates Its Inflammasome Activity
Open accessAbstract
NLRP3 assembles an inflammasome complex that activates caspase-1 upon sensing various danger signals derived from pathogenic infection, tissue damage, and environmental toxins. How NLRP3 senses these various stimuli is still poorly understood, but mitochondria and mitochondrial reactive oxygen species have been proposed to play a critical role in NLRP3 activation. In this article, we provide evidence that the mitochondrial antiviral signaling protein MAVS associates with NLRP3 and facilitates its oligomerization leading to caspase-1 activation. In reconstituted 293T cells, full-length MAVS promoted NLRP3-dependent caspase-1 activation, whereas a C-terminal transmembrane domain–truncated mutant of MAVS (MAVS-ΔTM) did not. MAVS, but not MAVS-ΔTM, interacted with NLRP3 and triggered the oligomerization of NLRP3, suggesting that mitochondrial localization of MAVS and intact MAVS signaling are essential for activating the NLRP3 inflammasome. Supporting this, activation of MAVS signaling by Sendai virus infection promoted NLRP3-dependent caspase-1 activation, whereas knocking down MAVS expression clearly attenuated the activation of NLRP3 inflammasome by Sendai virus in THP-1 and mouse macrophages. Taken together, our results suggest that MAVS facilitates the recruitment of NLRP3 to the mitochondria and may enhance its oligomerization and activation by bringing it in close proximity to mitochondrial reactive oxygen species.
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Cites
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Cited by
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
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Mechanism and Regulation of NLRP3 Inflammasome Activation
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Mitochondria are the powerhouses of immunity
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Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Del Re, D. P., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 961
Metadata
- Authors
- Park, S., Juliana, C., Hong, S., Datta, P., Hwang, I., Fernandes-Alnemri, T., Yu, J.-W., & Alnemri, E. S.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10
- Volume
- 191
- Issue
- 8
- Pages
- 4358-4366
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2138996282
- Cited by
- 266
- References
- 13
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- green
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- Park, S., Juliana, C., Hong, S., Datta, P., Hwang, I., Fernandes-Alnemri, T., Yu, J.-W., & Alnemri, E. S. (2013). The Mitochondrial Antiviral Protein MAVS Associates with NLRP3 and Regulates Its Inflammasome Activity. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1301170
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