[HTML][HTML] mTORC1 induced HK1-dependent glycolysis regulates NLRP3 inflammasome activation

JS Moon, S Hisata, MA Park, GM DeNicola, SW Ryter… - Cell reports, 2015 - ncbi.nlm.nih.gov
JS Moon, S Hisata, MA Park, GM DeNicola, SW Ryter, K Nakahira, AMK Choi
Cell reports, 2015ncbi.nlm.nih.gov
The mammalian target of rapamycin complex 1 (mTORC1) regulates activation of immune
cells and cellular energy metabolism. While glycolysis has been linked to immune functions,
the mechanisms by which glycolysis regulates NLRP3 inflammasome activation remain
unclear. Here, we demonstrate that mTORC1-induced glycolysis provides an essential
mechanism for NLRP3 inflammasome activation. Moreover, we demonstrate that
hexokinase 1 (HK1)-dependent glycolysis, under the regulation of mTORC1, represents a …
Summary
The mammalian target of rapamycin complex 1 (mTORC1) regulates activation of immune cells and cellular energy metabolism. While glycolysis has been linked to immune functions, the mechanisms by which glycolysis regulates NLRP3 inflammasome activation remain unclear. Here, we demonstrate that mTORC1-induced glycolysis provides an essential mechanism for NLRP3 inflammasome activation. Moreover, we demonstrate that hexokinase 1 (HK1)-dependent glycolysis, under the regulation of mTORC1, represents a critical metabolic pathway for NLRP3 inflammasome activation. Downregulation of glycolysis by inhibition of Raptor/mTORC1 or HK1 suppressed both pro-IL-1 β maturation and caspase-1 activation in macrophages in response to LPS and ATP. These results suggest that upregulation of HK1-dependent glycolysis by mTORC1 regulates NLRP3 inflammasome activation.
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