The coenzyme nicotinamide adenine dinucleotide phosphate (NADP⁺) and its reduced form (NADPH) regulate reductive metabolism in a subcellularly compartmentalized manner. Mitochondrial NADP(H) production depends on the phosphorylation of NAD(H) by NAD kinase 2 (NADK2). Deletion of NADK2 in human cell lines did not alter mitochondrial folate pathway activity, tricarboxylic acid cycle activity, or mitochondrial oxidative stress, but rather led to impaired cell proliferation in minimal medium. This growth defect was rescued by proline supplementation. NADK2-mediated mitochondrial NADP(H) generation was required for the reduction of glutamate and hence proline biosynthesis. Furthermore, mitochondrial NADP(H) availability determined the production of collagen proteins by cells of mesenchymal lineage. Thus, a primary function of the mitochondrial NADP(H) pool is to support proline biosynthesis for use in cytosolic protein synthesis.

辅酶烟酰胺腺嘌呤二核苷酸磷酸 (NADP ⁺ ) 及其还原形式 (NADPH) 以亚细胞区室化的方式调节还原代谢。线粒体 NADP(H) 的产生取决于 NAD 激酶 2 (NADK2) 对 NAD(H) 的磷酸化。删除NADK2在人类细胞系中，没有改变线粒体叶酸途径活性、三羧酸循环活性或线粒体氧化应激，而是导致基本培养基中细胞增殖受损。补充脯氨酸可以挽救这种生长缺陷。NADK2 介导的线粒体 NADP(H) 生成是减少谷氨酸和脯氨酸生物合成所必需的。此外，线粒体 NADP(H) 的可用性决定了间充质谱系细胞产生的胶原蛋白。因此，线粒体 NADP(H) 池的主要功能是支持脯氨酸生物合成以用于胞质蛋白合成。