mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation. Academic Article uri icon

Overview

MeSH

  • Animals
  • Caspase 1
  • Cells, Cultured
  • Interleukin-1beta
  • Macrophages
  • Mice

MeSH Major

  • Carrier Proteins
  • Glycolysis
  • Hexokinase
  • Inflammasomes
  • Multiprotein Complexes
  • TOR Serine-Threonine Kinases

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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

publication date

  • July 7, 2015

has subject area

  • Animals
  • Carrier Proteins
  • Caspase 1
  • Cells, Cultured
  • Glycolysis
  • Hexokinase
  • Inflammasomes
  • Interleukin-1beta
  • Macrophages
  • Mice
  • Multiprotein Complexes
  • TOR Serine-Threonine Kinases

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2015.05.046

PubMed ID

  • 26119735

Additional Document Info

start page

  • 102

end page

  • 115

volume

  • 12

number

  • 1