期刊
IMMUNITY
卷 48, 期 3, 页码 542-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2018.02.012
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资金
- SNSF [31003A_172848, CRSII3_160766, 323530_139181, PP00P3_144863]
- Basel University
- MRC [MC_UU_12022/6] Funding Source: UKRI
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 3b (GSK3 beta) at mito-chondria-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-gamma (IFN-gamma) in memory T cells. Subcellular organization of mTORC2-AKTGSK3 beta 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.
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