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线粒体产生的NADP(H)是脯氨酸合成的关键
作者:小柯机器人 发布时间:2021/4/23 12:32:28

美国斯隆-凯特琳癌症中心Craig B. Thompson团队发现,线粒体产生的NADP(H)是脯氨酸合成的关键。该研究于2021年4月22日在线发表于国际一流学术期刊《科学》。

研究人员表示,哺乳动物细胞依赖烟酰胺腺嘌呤二核苷酸磷酸分子在氧化形式(NADP+)和还原形式(NADPH)之间的相互转化,从而支持还原性生物合成并维持细胞内的抗氧化防御能力。NADP+和NADPH分子[此后称为NADP(H)]无法穿过亚细胞膜,因此被分隔开。线粒体NADP(H)的产生取决于NAD激酶2(NADK2)对NAD(H)的磷酸化作用。  

研究人员发现,在人类细胞系中敲除NADK2不会改变线粒体的叶酸途径活性、三羧酸循环活性或线粒体的氧化应激,但会导致在基本培养基中的细胞增殖受损。该生长缺陷通过补充脯氨酸得以挽救。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胶原蛋白的能力。因此,线粒体NADP(H)库的主要功能是支持脯氨酸生物合成来用于胞质蛋白的合成。

附:英文原文

Title: Mitochondrial NADP(H) generation is essential for proline biosynthesis

Author: Jiajun Zhu, Simon Schwrer, Mirela Berisa, Yeon Ju Kyung, Keun Woo Ryu, Junmei Yi, Xuejun Jiang, Justin R. Cross, Craig B. Thompson

Issue&Volume: 2021/04/22

Abstract: 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 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.

DOI: 10.1126/science.abd5491

Source: https://science.sciencemag.org/content/early/2021/04/21/science.abd5491

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037