Repository logo

PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells.

Published version



Change log


Finlay, David K 
Rosenzweig, Ella 
Sinclair, Linda V 
Feijoo-Carnero, Carmen 
Hukelmann, Jens L 


mTORC1 (mammalian target of rapamycin complex 1) controls transcriptional programs that determine CD8+ cytolytic T cell (CTL) fate. In some cell systems, mTORC1 couples phosphatidylinositol-3 kinase (PI3K) and Akt to the control of glucose uptake and glycolysis. However, PI3K-Akt-independent mechanisms control glucose metabolism in CD8+ T cells, and the role of mTORC1 has not been explored. The present study now demonstrates that mTORC1 activity in CD8+ T cells is not dependent on PI3K or Akt but is critical to sustain glucose uptake and glycolysis in CD8+ T cells. We also show that PI3K- and Akt-independent pathways mediated by mTORC1 regulate the expression of HIF1 (hypoxia-inducible factor 1) transcription factor complex. This mTORC1-HIF1 pathway is required to sustain glucose metabolism and glycolysis in effector CTLs and strikingly functions to couple mTORC1 to a diverse transcriptional program that controls expression of glucose transporters, multiple rate-limiting glycolytic enzymes, cytolytic effector molecules, and essential chemokine and adhesion receptors that regulate T cell trafficking. These data reveal a fundamental mechanism linking nutrient and oxygen sensing to transcriptional control of CD8+ T cell differentiation.



3-Phosphoinositide-Dependent Protein Kinases, Animals, Aryl Hydrocarbon Receptor Nuclear Translocator, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Movement, Chemokines, Gene Expression Regulation, Glucose, Glycolysis, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Interleukin-2, Mechanistic Target of Rapamycin Complex 1, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Multiprotein Complexes, Phosphatidylinositol 3-Kinases, Protein Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins c-akt, Receptors, Antigen, T-Cell, Receptors, Chemokine, TOR Serine-Threonine Kinases

Journal Title

J Exp Med

Conference Name

Journal ISSN


Volume Title



Rockefeller University Press