Dihydroorotate dehydrogenase (DHODH) is an enzyme of the de novo pyrimidine synthesis pathway that provides nucleotides for RNA/DNA synthesis essential for proliferation. In mammalian cells, DHODH is localized in mitochondria, linked to the respiratory chain via the coenzyme Q pool. Here we discuss the role of DHODH in the oxidative phosphorylation system and in the initiation and progression of cancer. We summarize recent findings on DHODH biology, the progress made in the development of new, specific inhibitors of DHODH intended for cancer therapy, and the mechanistic insights into the consequences of DHODH inhibition.

中文翻译：

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二氢乳清酸脱氢酶在氧化磷酸化和癌症中的作用

二氢乳清酸脱氢酶（DHODH）是从头嘧啶合成途径的酶，可为增殖所必需的RNA / DNA合成提供核苷酸。在哺乳动物细胞中，DHODH位于线粒体中，并通过辅酶Q库连接到呼吸链。在这里，我们讨论了DHODH在氧化磷酸化系统以及癌症的发生和发展中的作用。我们总结了有关DHODH生物学的最新发现，用于癌症治疗的新型DHODH特异性抑制剂的开发进展以及DHODH抑制作用的机理见解。