Mitochondrial NADP(H) generation is essential for proline biosynthesis

doi:10.1126/science.abd5491

GSTDTAP > 气候变化

DOI	10.1126/science.abd5491
	Mitochondrial NADP(H) generation is essential for proline biosynthesis
	Jiajun Zhu; Simon Schwörer; Mirela Berisa; Yeon Ju Kyung; Keun Woo Ryu; Junmei Yi; Xuejun Jiang; Justin R. Cross; Craig B. Thompson
	2021-05-28
发表期刊	Science
出版年	2021
英文摘要	Compartmentalization of metabolic processes into organelles can have important consequences. Zhu et al. examined the role of the coenzyme nicotinamide adenine dinucleotide phosphate (NADP+) and its reduced form (NADPH) in cultured human cells. They found that cells lacking NAD kinase 2, an enzyme needed to make NADPH, had decreased abundance of mitochondrial NADPH and proliferated slowly in culture medium with limited nutrients because of a lack of proline. Proline is made in the mitochondria, and thus a key function of NADPH in the mitochondria appears to be the synthesis of proline to sustain cellular protein synthesis. Science , abd5491, this issue p. [968][1] 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. [1]: /lookup/doi/10.1126/science.abd5491
领域	气候变化 ; 资源环境
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/328868
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jiajun Zhu,Simon Schwörer,Mirela Berisa,et al. Mitochondrial NADP(H) generation is essential for proline biosynthesis[J]. Science,2021.
APA	Jiajun Zhu.,Simon Schwörer.,Mirela Berisa.,Yeon Ju Kyung.,Keun Woo Ryu.,...&Craig B. Thompson.(2021).Mitochondrial NADP(H) generation is essential for proline biosynthesis.Science.
MLA	Jiajun Zhu,et al."Mitochondrial NADP(H) generation is essential for proline biosynthesis".Science (2021).