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

Autor:	Bantug GR; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Fischer M; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Grählert J; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Balmer ML; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Unterstab G; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Develioglu L; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Steiner R; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Zhang L; Ludwig Center for Cancer Research, University of Lausanne. 155 Chemin des Boveresses, Épalinges, 1066 Vaud, Switzerland., Costa ASH; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, University of Cambridge, Box 197, Cambridge Biomedical Campus, CB2 0XZ Cambridge, UK., Gubser PM; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Burgener AV; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Sauder U; Electron Microscopy Core Facility, Biozentrum, University of Basel, 70 Klingelbergstrasse, 4056 Basel, Switzerland., Löliger J; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Belle R; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Dimeloe S; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Lötscher J; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Jauch A; Immunodeficiency Laboratory, Department of Biomedicine, University and University Hospital of Basel, 20 Hebelstrasse, 4031 Basel, Switzerland., Recher M; Immunodeficiency Laboratory, Department of Biomedicine, University and University Hospital of Basel, 20 Hebelstrasse, 4031 Basel, Switzerland., Hönger G; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland., Hall MN; Biozentrum, University of Basel, 70 Klingelbergstrasse, 4056 Basel, Switzerland., Romero P; Ludwig Center for Cancer Research, University of Lausanne. 155 Chemin des Boveresses, Épalinges, 1066 Vaud, Switzerland., Frezza C; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, University of Cambridge, Box 197, Cambridge Biomedical Campus, CB2 0XZ Cambridge, UK., Hess C; Immunobiology Laboratory, Department of Biomedicine, University and University Hospital of Basel. 20 Hebelstrasse, 4031 Basel, Switzerland. Electronic address: chess@uhbs.ch.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2018 Mar 20; Vol. 48 (3), pp. 542-555.e6. Date of Electronic Publication: 2018 Mar 06.
DOI:	10.1016/j.immuni.2018.02.012
Abstrakt:	Glycolysis is linked to the rapid response of memory CD8 + T cells, but the molecular and subcellular structural elements enabling enhanced glucose metabolism in nascent activated memory CD8 + 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 + T cells to rapidly acquire effector function. (Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu