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

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 interfero

SUBMITTER: Bantug GR 

PROVIDER: S-EPMC6049611 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature