Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8<sup>+</sup> T Cells.

Details

Serval ID
serval:BIB_860F1556AA95
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8<sup>+</sup> T Cells.
Journal
Immunity
Author(s)
Bantug G.R., Fischer M., Grählert J., Balmer M.L., Unterstab G., Develioglu L., Steiner R., Zhang L., Costa ASH, Gubser P.M., Burgener A.V., Sauder U., Löliger J., Belle R., Dimeloe S., Lötscher J., Jauch A., Recher M., Hönger G., Hall M.N., Romero P., Frezza C., Hess C.
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Publication state
Published
Issued date
20/03/2018
Peer-reviewed
Oui
Volume
48
Number
3
Pages
542-555.e6
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Glycolysis is linked to the rapid response of memory CD8 <sup>+</sup> T cells, but the molecular and subcellular structural elements enabling enhanced glucose metabolism in nascent activated memory CD8 <sup>+</sup> T cells are unknown. We found that rapid activation of protein kinase B (PKB or AKT) by mammalian target of rapamycin complex 2 (mTORC2) led to inhibition of glycogen synthase kinase 3β (GSK3β) at mitochondria-endoplasmic reticulum (ER) junctions. This enabled recruitment of hexokinase I (HK-I) to the voltage-dependent anion channel (VDAC) on mitochondria. Binding of HK-I to VDAC promoted respiration by facilitating metabolite flux into mitochondria. Glucose tracing pinpointed pyruvate oxidation in mitochondria, which was the metabolic requirement for rapid generation of interferon-γ (IFN-γ) in memory T cells. Subcellular organization of mTORC2-AKT-GSK3β at mitochondria-ER contact sites, promoting HK-I recruitment to VDAC, thus underpins the metabolic reprogramming needed for memory CD8 <sup>+</sup> T cells to rapidly acquire effector function.
Keywords
CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Cell Respiration, Endoplasmic Reticulum/metabolism, Endoplasmic Reticulum/ultrastructure, Energy Metabolism, Glycogen Synthase Kinase 3 beta/metabolism, Glycolysis, Immunologic Memory, Intracellular Membranes/metabolism, Lymphocyte Activation, Mechanistic Target of Rapamycin Complex 2/metabolism, Mitochondria/metabolism, Mitochondria/ultrastructure, Models, Biological, Proto-Oncogene Proteins c-akt/metabolism, Rapamycin-Insensitive Companion of mTOR Protein/deficiency, Signal Transduction, Akt, GSK3-beta, IFN-gamma, VDAC, endoplasmic reticulum, glycolysis, hexokinase, mTOR, memory CD8(+) T cells, mitochondria
Pubmed
Web of science
Create date
15/03/2018 18:54
Last modification date
20/08/2019 14:45
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