title: T lymphocyte regulation by mevalonate metabolism.
abstract: Whereas resting T cells, which have low metabolic requirements, use oxidative phosphorylation (OXPHOS) to maximize their generation of ATP, activated T cells, similar to tumor cells, shift metabolic activity to aerobic glycolysis, which also fuels mevalonate metabolism. Both sterol and nonsterol derivatives of mevalonate affect T cell function. The intracellular availability of sterols, which is dynamically regulated by different classes of transcription factors, represents a metabolic checkpoint that modulates T cell responses. The electron carrier ubiquinone, which is modified with an isoprenoid membrane anchor, plays a pivotal role in OXPHOS, which supports the proliferation of T cells. Isoprenylation also mediates the plasma membrane attachment of the Ras, Rho, and Rab guanosine triphosphatases, which are involved in T cell immunological synapse formation, migration, proliferation, and cytotoxic effector responses. Finally, multiple phosphorylated mevalonate derivatives can act as danger signals for innate-like γδ T cells, thus contributing to the immune surveillance of stress, pathogens, and tumors. We highlight the importance of the mevalonate pathway in the metabolic reprogramming of effector and regulatory T cells.
authors.affiliation: Immunotherapy Unit, Department of Urology, Medical University of Innsbruck and Oncotyrol, K1 Center for Personalized Cancer Medicine, 6020 Innsbruck, Austria. martin.thurnher@i-med.ac.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Thurnher
authors.affiliation: Immunotherapy Unit, Department of Urology, Medical University of Innsbruck and Oncotyrol, K1 Center for Personalized Cancer Medicine, 6020 Innsbruck, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Gruenbacher
mesh_terms: D002784:Cholesterol / Q000378:metabolism; D006019:Glycolysis; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D053858:Metabolic Networks and Pathways / Q000276:immunology*; D008798:Mevalonic Acid / Q000378:metabolism*; D018448:Models, Immunological; D010085:Oxidative Phosphorylation; D017368:Protein Prenylation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D012739:Gonadal Steroid Hormones; D014451:Ubiquinone; D002784:Cholesterol; D008798:Mevalonic Acid