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

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

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DOI	10.1097/IN9.0000000000000019
刊名	Immunometabolism IJ
年，卷(期)	2023, 5(1)
作者	Peeters, Marlies J. W.; Desler, Claus; Straten, Per Thor,
作者单位	[Peeters, Marlies J. W.; Straten, Per Thor] Copenhagen Univ Hosp Herlev, Natl Ctr Canc Immune Therapy, Dept Oncol, Copenhagen, Denmark; [Desler, Claus] Univ Copenhagen, Ctr Hlth Aging, Dept Cellular & Mol Med, Copenhagen, Denmark; [Straten, Per Thor] Univ
摘要	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.
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.
关键词	T cell metabolism; T cell activation; de novo pyrimidine synthesis; mitochondrial respiration and oxidative respiration
KeyWord	T cell metabolism; T cell activation; de novo pyrimidine synthesis; mitochondrial respiration and oxidative respiration
基金项目
页码	1-5

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引用本文

Peeters, Marlies J. W.; Desler, Claus; Straten, Per Thor. Mitochondrial-linked de novo pyrimidine synthesis as a regulator of T cell responses [J]. Immunometabolism. 2023; 5; (1). 1 - 5.

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