T lymphocyte regulation by mevalonate metabolism.

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.
AuthorsMartin Thurnher, Georg Gruenbacher
JournalScience signaling (Sci Signal) Vol. 8 Issue 370 Pg. re4 (Mar 31 2015) ISSN: 1937-9145 [Electronic] United States
PMID25829448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2015, American Association for the Advancement of Science.
Chemical References
  • Gonadal Steroid Hormones
  • Ubiquinone
  • Cholesterol
  • Mevalonic Acid
  • Cholesterol (metabolism)
  • Glycolysis
  • Gonadal Steroid Hormones (metabolism)
  • Homeostasis (immunology)
  • Humans
  • Lymphocyte Activation (immunology)
  • Metabolic Networks and Pathways (immunology)
  • Mevalonic Acid (metabolism)
  • Models, Immunological
  • Oxidative Phosphorylation
  • Protein Prenylation (immunology)
  • T-Lymphocytes (immunology, metabolism)
  • Ubiquinone (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: