MTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation

Jong Seok Moon, Shu Hisata, Mi Ae Park, Gina M. DeNicola, Stefan W. Ryter, Kiichi Nakahira, Augustine M.K. Choi

Research output: Contribution to journalArticlepeer-review

316 Scopus citations


The mammalian target of rapamycin complex 1 (mTORC1) regulates activation of immune cells and cellular energy metabolism. Although glycolysis has been linked to immune functions, the mechanisms by which glycolysis regulates NLRP3 inflammasome activation remain unclear. Here, wedemonstrate thatmTORC1-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 ofRaptor/mTORC1 or HK1 suppressed both pro-IL-1β 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.

Original languageEnglish (US)
Pages (from-to)102-115
Number of pages14
JournalCell Reports
Issue number1
StatePublished - Jul 7 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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