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
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
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 19:54
Last modification date
20/08/2019 15:45