The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation

• DOI: 10.1242/jcs.124388
• Publication Date: 2013-04-24T03:37:18Z
• Authors: Kathy Triantafilou; Timothy R. Hughes; Martha Triantafilou; B. Paul Morgan
• Keywords: Uniporter; Calcium in biology

The membrane attack complex of complement (MAC), apart from its classical role lysing cells, can also trigger a range non-lethal effects on acting as drive to inflammation. In the present study, we chose investigate these inflammasome activation. We found that, following sublytic MAC attack, there is increased cytosolic Ca(2+) concentration, at least partly through release endoplasmic reticulum lumen via inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine (RyR) channels. This increase in intracellular concentration leads accumulation mitochondrial matrix 'mitochondrial calcium uniporter' (MCU), loss transmembrane potential, triggering NLRP3 activation IL-1β release. co-localises with mitochondria, probably sensing resultant dysfunction, leading caspase apoptosis. first study that links provides mechanism by which inflammation