Mitochondrial-linked de novo pyrimidine synthesis as a regulator of T cell responses

Marlies J.W. Peeters*, Claus Desler, Per Thor Straten

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

1 Citation (Scopus)
17 Downloads (Pure)

Abstract

It has been well established that the metabolism of T cells is integral to their functionality. If a T cell cannot generate enough energy or building blocks, it will not be able to exert its cytotoxic properties to eliminate pathogens and cancer cells. Impairment of mitochondrial oxidative phosphorylation is a well-known disruptor of T cell activation. Dihydroorotate dehydrogenase (DHODH) is a rate-limiting component of the de novo synthesis of pyrimidines and its activity is dependent on functional mitochondrial oxidative phosphorylation. In this regard, DHODH inhibitors have long been used in clinical settings for the treatment of autoimmune diseases, as they potently inhibit lymphocyte proliferation. The exact mode-of-Action of these inhibitors in T lymphocytes is not yet exactly understood. In this review, we briefly discuss the critical role of mitochondria in T cell functionality. We also describe how de novo pyrimidine biosynthesis is linked to mitochondrial activity. Finally, we summarize our current knowledge of how mitochondrial-linked de novo pyrimidine biosynthesis modulates T cell responses.

Original languageEnglish
Article numberE00019
JournalImmunometabolism (United States)
Volume5
Issue number1
Number of pages5
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 The Author(s), Published by Wolters Kluwer Health, Inc.

Keywords

  • de novo pyrimidine synthesis
  • mitochondrial respiration and oxidative respiration
  • T cell activation
  • T cell metabolism

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