RETRACTED: mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation (Retracted article.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

[1]

[Anonymous], 2009, Science

[2]

ARORA KK, 1990, J BIOL CHEM, V265, P6481

[3]

Azoulay-Zohar H, 2000, EUR J BIOCHEM, V267, P2973

[4] Binding of rat brain hexokinase to recombinant yeast mitochondria: Identification of necessary molecular determinants [J].

Azoulay-Zohar, H ;

Aflalo, C .

JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1999, 31 (06) :569-579

[5] RESIDUES PUTATIVELY INVOLVED IN BINDING OF ATP AND GLUCOSE-6-PHOSPHATE TO A MAMMALIAN HEXOKINASE - SITE-DIRECTED MUTATION AT ANALOGOUS POSITIONS IN THE N-TERMINAL AND C-TERMINAL HALVES OF THE TYPE-I ISOZYME [J].

BAIJAL, M ;

WILSON, JE .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1995, 321 (02) :413-420

[6] Rapamycin passes the torch: a new generation of mTOR inhibitors [J].

Benjamin, Don ;

Colombi, Marco ;

Moroni, Christoph ;

Hall, Michael N. .

NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (11) :868-880

[7] Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth [J].

Bruchard, Melanie ;

Mignot, Gregoire ;

Derangere, Valentin ;

Chalmin, Fanny ;

Chevriaux, Angelique ;

Vegran, Frederique ;

Boireau, Wilfrid ;

Simon, Benoit ;

Ryffel, Bernhard ;

Connat, Jean Louis ;

Kanellopoulos, Jean ;

Martin, Francois ;

Rebe, Cedric ;

Apetoh, Lionel ;

Ghiringhelli, Francois .

NATURE MEDICINE, 2013, 19 (01) :57-64

[8]

BUSTAMANTE E, 1981, J BIOL CHEM, V256, P8699

[9] Regulation of cancer cell metabolism [J].

Cairns, Rob A. ;

Harris, Isaac S. ;

Mak, Tak W. .

NATURE REVIEWS CANCER, 2011, 11 (02) :85-95

[10]

CRANE RK, 1953, J BIOL CHEM, V203, P273

← 1 2 3 4 5 →