Triantafilou, K.  ORCID: https://orcid.org/0000-0002-7473-6278, Hughes, T. R. ORCID: https://orcid.org/0000-0003-2348-3490, Triantafilou, M. ORCID: https://orcid.org/0000-0002-7473-6278 and Morgan, B. P. ORCID: https://orcid.org/0000-0003-4075-7676
2013.
The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation.
Journal of Cell Science
126
(13)
, pp. 2903-2913.
10.1242/jcs.124388
|
Abstract
The membrane attack complex of complement (MAC), apart from its classical role of lysing cells, can also trigger a range of non-lethal effects on cells, acting as a drive to inflammation. In the present study, we chose to investigate these non-lethal effects on inflammasome activation. We found that, following sublytic MAC attack, there is increased cytosolic Ca2+ concentration, at least partly through Ca2+ release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) channels. This increase in intracellular Ca2+ concentration leads to Ca2+ accumulation in the mitochondrial matrix via the ‘mitochondrial calcium uniporter’ (MCU), and loss of mitochondrial transmembrane potential, triggering NLRP3 inflammasome activation and IL-1β release. NLRP3 co-localises with the mitochondria, probably sensing the increase in calcium and the resultant mitochondrial dysfunction, leading to caspase activation and apoptosis. This is the first study that links non-lethal effects of sublytic MAC attack with inflammasome activation and provides a mechanism by which sublytic MAC can drive inflammation and apoptosis.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | Published |
| Schools: | Schools > Medicine |
| Publisher: | Company of Biologists |
| ISSN: | 0021-9533 |
| Date of Acceptance: | 27 March 2013 |
| Last Modified: | 24 Oct 2022 08:04 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/116742 |
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