Glucose-Induced Activation of mTORC1 is Associated with Hexokinase2 Binding to Sestrins in HEK293T Cells.
glucose
mTORC1
metabolism
nutrient signaling
skeletal muscle
Journal
The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
29
07
2022
revised:
25
10
2022
accepted:
23
11
2022
pmc-release:
22
12
2023
medline:
18
4
2023
entrez:
15
4
2023
pubmed:
16
4
2023
Statut:
ppublish
Résumé
Sestrins (SESN1-3) act as proximal sensors in leucine-induced activation of the protein kinase mechanistic target of rapamycin (mTOR) in complex 1 (mTORC1), a key regulator of cell growth and metabolism. In the present study, the hypothesis that SESNs also mediate glucose-induced activation of mTORC1 was tested. Rats underwent overnight fasting, and in the morning, either saline or a glucose solution (4 g⋅kg Glucose administration to fasted rats promoted mTORC1 activation. Similarly, glucose readdition (GluAB) to the medium of glucose-deprived WT cells also promoted mTORC1 activation. By contrast, SESNTKO cells demonstrated attenuated mTORC1 activation following GluAB compared with WT cells. Interestingly, HK2 associated with all 3 SESNs in a glucose-dependent manner, i.e., HK2 abundance in SESN immunoprecipitates was high in cells deprived of glucose and decreased in response to GluAB. Moreover, similar to SESNTKO cells, the sensitivity of mTORC1 to GluAB was attenuated in HK2KO cells compared with WT cells. The results of this study demonstrate that the SESNs and HK2 play important roles in glucose-induced mTORC1 activation in HEK293T cells. However, unlike leucine-induced mTORC1 activation, the effect was independent of the changes in SESN-GATOR2 interaction, and instead, it was associated with alterations in the association of SESNs with HK2.
Sections du résumé
BACKGROUND
Sestrins (SESN1-3) act as proximal sensors in leucine-induced activation of the protein kinase mechanistic target of rapamycin (mTOR) in complex 1 (mTORC1), a key regulator of cell growth and metabolism.
OBJECTIVE
In the present study, the hypothesis that SESNs also mediate glucose-induced activation of mTORC1 was tested.
METHODS
Rats underwent overnight fasting, and in the morning, either saline or a glucose solution (4 g⋅kg
RESULTS
Glucose administration to fasted rats promoted mTORC1 activation. Similarly, glucose readdition (GluAB) to the medium of glucose-deprived WT cells also promoted mTORC1 activation. By contrast, SESNTKO cells demonstrated attenuated mTORC1 activation following GluAB compared with WT cells. Interestingly, HK2 associated with all 3 SESNs in a glucose-dependent manner, i.e., HK2 abundance in SESN immunoprecipitates was high in cells deprived of glucose and decreased in response to GluAB. Moreover, similar to SESNTKO cells, the sensitivity of mTORC1 to GluAB was attenuated in HK2KO cells compared with WT cells.
CONCLUSIONS
The results of this study demonstrate that the SESNs and HK2 play important roles in glucose-induced mTORC1 activation in HEK293T cells. However, unlike leucine-induced mTORC1 activation, the effect was independent of the changes in SESN-GATOR2 interaction, and instead, it was associated with alterations in the association of SESNs with HK2.
Identifiants
pubmed: 37061344
pii: S0022-3166(22)13243-8
doi: 10.1016/j.tjnut.2022.11.021
pmc: PMC10273196
pii:
doi:
Substances chimiques
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Leucine
GMW67QNF9C
Sestrins
0
Hexokinase
EC 2.7.1.1
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
988-998Subventions
Organisme : NIDDK NIH HHS
ID : F32 DK126312
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK015658
Pays : United States
Organisme : NIAAA NIH HHS
ID : R37 AA011290
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.
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