Mitochondrial NADP(H) generation is essential for proline biosynthesis Research Letter
| Authors: | Zhu, J.; Schwörer, S.; Berisa, M.; Kyung, Y. J.; Ryu, K. W.; Yi, J.; Jiang, X.; Cross, J. R.; Thompson, C. B. |
| Title: | Mitochondrial NADP(H) generation is essential for proline biosynthesis |
| 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 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. © 2021 American Association for the Advancement of Science. All rights reserved. |
| Keywords: | genetics; cell proliferation; mouse; animal; metabolism; animals; mice; culture medium; cell line; protein; enzyme activity; cell line, tumor; biosynthesis; nude mouse; mice, nude; phosphotransferases (alcohol group acceptor); tumor cell line; collagen; oxidative stress; folic acid; glutamic acid; mitochondrial protein; mitochondria; phosphate; phosphotransferase; mitochondrion; cytosol; glutathione; culture media; proline; enzyme; growth; cell; nadp; citric acid cycle; mitochondrial proteins; gene knockout techniques; nicotinamide adenine dinucleotide phosphate; humans; human; female; metabolome; gene knockout; nadk2 protein, human |
| Journal Title: | Science |
| Volume: | 372 |
| Issue: | 6545 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2021-05-28 |
| Start Page: | 968 |
| End Page: | 972 |
| Language: | English |
| DOI: | 10.1126/science.abd5491 |
| PUBMED: | 33888598 |
| PROVIDER: | scopus |
| PMCID: | PMC8241437 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2021 -- Source: Scopus |
