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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.
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
Topics
  • 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)

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