PMID- 35305311
OWN - NLM
STAT- MEDLINE
DCOM- 20220412
LR  - 20230722
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 82
IP  - 7
DP  - 2022 Apr 7
TI  - Hexokinase 1 cellular localization regulates the metabolic fate of glucose.
PG  - 1261-1277.e9
LID - S1097-2765(22)00166-6 [pii]
LID - 10.1016/j.molcel.2022.02.028 [doi]
AB  - The product of hexokinase (HK) enzymes, glucose-6-phosphate, can be metabolized 
      through glycolysis or directed to alternative metabolic routes, such as the 
      pentose phosphate pathway (PPP) to generate anabolic intermediates. HK1 contains 
      an N-terminal mitochondrial binding domain (MBD), but its physiologic 
      significance remains unclear. To elucidate the effect of HK1 mitochondrial 
      dissociation on cellular metabolism, we generated mice lacking the HK1 MBD 
      (DeltaE1HK1). These mice produced a hyper-inflammatory response when challenged with 
      lipopolysaccharide. Additionally, there was decreased glucose flux below the 
      level of GAPDH and increased upstream flux through the PPP. The glycolytic block 
      below GAPDH is mediated by the binding of cytosolic HK1 with S100A8/A9, resulting 
      in GAPDH nitrosylation through iNOS. Additionally, human and mouse macrophages 
      from conditions of low-grade inflammation, such as aging and diabetes, displayed 
      increased cytosolic HK1 and reduced GAPDH activity. Our data indicate that HK1 
      mitochondrial binding alters glucose metabolism through regulation of GAPDH.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - De Jesus, Adam
AU  - De Jesus A
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Keyhani-Nejad, Farnaz
AU  - Keyhani-Nejad F
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Pusec, Carolina M
AU  - Pusec CM
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Department of Medicine, University of Illinois at 
      Chicago, Chicago, IL 60612, USA.
FAU - Goodman, Lauren
AU  - Goodman L
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Geier, Justin A
AU  - Geier JA
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Stoolman, Joshua S
AU  - Stoolman JS
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Stanczyk, Paulina J
AU  - Stanczyk PJ
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Nguyen, Tivoli
AU  - Nguyen T
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Xu, Kai
AU  - Xu K
AD  - Department of Biochemistry and Molecular Genetics, Northwestern University 
      Feinberg School of Medicine, Chicago, IL 60611, USA.
FAU - Suresh, Krishna V
AU  - Suresh KV
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Chen, Yihan
AU  - Chen Y
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Rodriguez, Arianne E
AU  - Rodriguez AE
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Shapiro, Jason S
AU  - Shapiro JS
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Chang, Hsiang-Chun
AU  - Chang HC
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Chen, Chunlei
AU  - Chen C
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Shah, Kriti P
AU  - Shah KP
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Ben-Sahra, Issam
AU  - Ben-Sahra I
AD  - Department of Biochemistry and Molecular Genetics, Northwestern University 
      Feinberg School of Medicine, Chicago, IL 60611, USA.
FAU - Layden, Brian T
AU  - Layden BT
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Department of Medicine, University of Illinois at 
      Chicago, Chicago, IL 60612, USA; Jesse Brown Veterans Affairs Medical Center, 
      Chicago, IL 60612, USA.
FAU - Chandel, Navdeep S
AU  - Chandel NS
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Weinberg, Samuel E
AU  - Weinberg SE
AD  - Department of Pathology, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Ardehali, Hossein
AU  - Ardehali H
AD  - Department of Medicine, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA; Feinberg Cardiovascular Research Institute, Northwestern 
      University, Chicago, IL 60611, USA. Electronic address: 
      h-ardehali@northwestern.edu.
LA  - eng
GR  - R01 HL140973/HL/NHLBI NIH HHS/United States
GR  - R01 DK104927/DK/NIDDK NIH HHS/United States
GR  - R01 HL138982/HL/NHLBI NIH HHS/United States
GR  - R01 HL127646/HL/NHLBI NIH HHS/United States
GR  - F31 HL132552/HL/NHLBI NIH HHS/United States
GR  - T32 GM008152/GM/NIGMS NIH HHS/United States
GR  - P30 DK020595/DK/NIDDK NIH HHS/United States
GR  - R01 HL140927/HL/NHLBI NIH HHS/United States
GR  - T32 GM144295/GM/NIGMS NIH HHS/United States
GR  - I01 BX003382/BX/BLRD VA/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220318
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - EC 2.7.1.1 (HK1 protein, mouse)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Trends Endocrinol Metab. 2022 Oct;33(10):665-667. PMID: 35953432
MH  - Animals
MH  - *Glucose/metabolism
MH  - Glycolysis
MH  - Hexokinase/genetics/*metabolism
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Pentose Phosphate Pathway
PMC - PMC8995391
MID - NIHMS1785747
OTO - NOTNLM
OT  - GAPDH
OT  - S-nitrosylation
OT  - hexokinase
OT  - inflammation
OT  - innate immunity
OT  - macrophage
OT  - metabolism
OT  - mitochondria
OT  - pentose phosphate pathway
OT  - subcellular localization
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2022/03/20 06:00
MHDA- 2022/04/13 06:00
PMCR- 2023/04/07
CRDT- 2022/03/19 20:05
PHST- 2021/01/11 00:00 [received]
PHST- 2021/10/12 00:00 [revised]
PHST- 2022/02/22 00:00 [accepted]
PHST- 2022/03/20 06:00 [pubmed]
PHST- 2022/04/13 06:00 [medline]
PHST- 2022/03/19 20:05 [entrez]
PHST- 2023/04/07 00:00 [pmc-release]
AID - S1097-2765(22)00166-6 [pii]
AID - 10.1016/j.molcel.2022.02.028 [doi]
PST - ppublish
SO  - Mol Cell. 2022 Apr 7;82(7):1261-1277.e9. doi: 10.1016/j.molcel.2022.02.028. Epub 
      2022 Mar 18.