Abstract:
: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.
journal_name
Immunityjournal_title
Immunityauthors
Bantug GR,Fischer M,Grählert J,Balmer ML,Unterstab G,Develioglu L,Steiner R,Zhang L,Costa ASH,Gubser PM,Burgener AV,Sauder U,Löliger J,Belle R,Dimeloe S,Lötscher J,Jauch A,Recher M,Hönger G,Hall MN,Romero P,Frezdoi
10.1016/j.immuni.2018.02.012subject
Has Abstractpub_date
2018-03-20 00:00:00pages
542-555.e6issue
3eissn
1074-7613issn
1097-4180pii
S1074-7613(18)30070-0journal_volume
48pub_type
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