title: mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation.
abstract: 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, 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-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.
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Moon
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Hisata
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Park
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Gina M
authors.initials: GM
authors.lastname: DeNicola
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Ryter
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Nakahira
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: amc2056@med.cornell.edu.
authors.forename: Augustine M K
authors.initials: AMK
authors.lastname: Choi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D046912:Multiprotein Complexes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C515658:HK1 protein, mouse; D006593:Hexokinase; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020170:Caspase 1