RETRACTED: mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation (Retracted article. See vol. 42, 2023)

被引：321

作者：

Moon, Jong-Seok ^{[1
,2
,3
]}

Hisata, Shu ^{[1
,2
,3
]}

Park, Mi-Ae ^{[4
]}

DeNicola, Gina M. ^{[1
,2
]}

Ryter, Stefan W. ^{[1
,2
,3
]}

Nakahira, Kiichi ^{[1
,2
,3
]}

Choi, Augustine M. K. ^{[1
,2
,3
]}

机构：

[1] Weill Cornell Med Coll, Joan & Sanford I Weill Dept Med, New York, NY 10065 USA

[2] New York Presbyterian Hosp, New York, NY 10065 USA

[3] Weill Cornell Med Coll, Div Pulm & Crit Care Med, New York, NY 10065 USA

[4] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA

来源：

CELL REPORTS | 2015年 / 12卷 / 01期

关键词：

RECOMBINANT YEAST MITOCHONDRIA; RAT-BRAIN HEXOKINASE; MAMMALIAN HEXOKINASE; TUMOR-CELLS; MTOR; METABOLISM; GLUCOSE; BINDING; LOCALIZATION; GROWTH;

D O I：

10.1016/j.celrep.2015.05.046

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-1 beta 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.

引用

页码：102 / 115

页数：14

共 47 条

[41] Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1 [J].

Tsukiyama-Kohara, K ;

Poulin, F ;

Kohara, M ;

DeMaria, CT ;

Cheng, A ;

Wu, ZD ;

Gingras, AC ;

Katsume, A ;

Elchebly, M ;

Spiegelman, BM ;

Harper, ME ;

Tremblay, ML ;

Sonenberg, N .

NATURE MEDICINE, 2001, 7 (10) :1128-1132

[42] The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance [J].

Vandanmagsar, Bolormaa ;

Youm, Yun-Hee ;

Ravussin, Anthony ;

Galgani, Jose E. ;

Stadler, Krisztian ;

Mynatt, Randall L. ;

Ravussin, Eric ;

Stephens, Jacqueline M. ;

Dixit, Vishwa Deep .

NATURE MEDICINE, 2011, 17 (02) :179-U214

[43] Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling [J].

Wen, Haitao ;

Gris, Denis ;

Lei, Yu ;

Jha, Sushmita ;

Zhang, Lu ;

Huang, Max Tze-Han ;

Brickey, Willie June ;

Ting, Jenny P-Y .

NATURE IMMUNOLOGY, 2011, 12 (05) :408-U61

[44] Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function [J].

Wilson, JE .

JOURNAL OF EXPERIMENTAL BIOLOGY, 2003, 206 (12) :2049-2057

[45] mTORC1 couples immune signals and metabolic programming to establish Treg-cell function [J].

Zeng, Hu ;

Yang, Kai ;

Cloer, Caryn ;

Neale, Geoffrey ;

Vogel, Peter ;

Chi, Hongbo .

NATURE, 2013, 499 (7459) :485-+

[46] A role for mitochondria in NLRP3 inflammasome activation [J].

Zhou, Rongbin ;

Yazdi, Amir S. ;

Menu, Philippe ;

Tschopp, Juerg .

NATURE, 2011, 469 (7329) :221-225

[47] Thioredoxin-interacting protein links oxidative stress to inflammasome activation [J].

Zhou, Rongbin ;

Tardivel, Aubry ;

Thorens, Bernard ;

Choi, Inpyo ;

Tschopp, Juerg .

NATURE IMMUNOLOGY, 2010, 11 (02) :136-U51

← 1 2 3 4 5 →