Mitochondrial NADP(H) generation is essential for proline biosynthesis
Jiajun Zhu, Simon Schwörer, Mirela Berisa, Yeon Ju Kyung, Keun Woo Ryu, Jun-Mei Yi, Xuejun Jiang, Justin R. Cross, Craig B. Thompson
Abstract
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.