RETRACTED: mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation (Retracted article.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

被引:322
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
收藏
页码:102 / 115
页数:14
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