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

doi:10.1016/j.celrep.2015.05.046

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 journal › Article › peer-review

317 Scopus citations

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, 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 language	English (US)
Pages (from-to)	102-115
Number of pages	14
Journal	Cell Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2015.05.046
State	Published - Jul 7 2015
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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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, 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.",

author = "Moon, {Jong Seok} and Shu Hisata and Park, {Mi Ae} and DeNicola, {Gina M.} and Ryter, {Stefan W.} and Kiichi Nakahira and Choi, {Augustine M.K.}",

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AU - Moon, Jong Seok

AU - Hisata, Shu

AU - Park, Mi Ae

AU - DeNicola, Gina M.

AU - Ryter, Stefan W.

AU - Nakahira, Kiichi

AU - Choi, Augustine M.K.

PY - 2015/7/7

Y1 - 2015/7/7

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AB - 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.

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MTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation

Abstract

ASJC Scopus subject areas

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