One-carbon (1C) metabolism encompasses folate-mediated 1C transfer reactions and related processes, including nucleotide and amino acid biosynthesis, antioxidant regeneration, and epigenetic regulation. 1C pathways are compartmentalized in the cytosol, mitochondria, and nucleus. 1C metabolism in the cytosol has been an important therapeutic target for cancer since the inception of modern chemotherapy, and “antifolates” targeting cytosolic 1C pathways continue to be a mainstay of the chemotherapy armamentarium for cancer. Recent insights into the complexities of 1C metabolism in cancer cells, including the critical role of the mitochondrial 1C pathway as a source of 1C units, glycine, reducing equivalents, and ATP, have spurred the discovery of novel compounds that target these reactions, with particular focus on 5,10-methylene tetrahydrofolate dehydrogenase 2 and serine hydroxymethyltransferase 2. In this review, we discuss key aspects of 1C metabolism, with emphasis on the importance of mitochondrial 1C metabolism to metabolic homeostasis, its relationship with the oncogenic phenotype, and its therapeutic potential for cancer.

中文翻译：

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癌症中线粒体一碳代谢的治疗靶向

一碳 (1C) 代谢包括叶酸介导的 1C 转移反应和相关过程，包括核苷酸和氨基酸生物合成、抗氧化剂再生和表观遗传调控。1C 通路在胞质溶胶、线粒体和细胞核中被划分。自现代化学疗法问世以来，细胞质中的 1C 代谢一直是癌症的重要治疗靶点，而靶向细胞质 1C 途径的“抗叶酸剂”仍然是癌症化学疗法的中流砥柱。最近对癌细胞中 1C 代谢复杂性的见解，包括线粒体 1C 途径作为 1C 单位、甘氨酸、还原当量和 ATP 来源的关键作用，促进了针对这些反应的新化合物的发现，特别是专注于5，