Mitochondrial NADP⁺ is essential for proline biosynthesis during cell growth.

ABSTRACT: Nicotinamide adenine dinucleotide phosphate (NADP⁺) is vital to produce NADPH, a principal supplier of reducing power for biosynthesis of macromolecules and protection against oxidative stress. NADPH exists in separate pools, in both the cytosol and mitochondria; however, the cellular functions of mitochondrial NADPH are incompletely described. Here, we find that decreasing mitochondrial NADP(H) levels through depletion of NAD kinase 2 (NADK2), an enzyme responsible for production of mitochondrial NADP⁺, renders cells uniquely proline auxotrophic. Cells with NADK2 deletion fail to synthesize proline, due to mitochondrial NADPH deficiency. We uncover the requirement of mitochondrial NADPH and NADK2 activity for the generation of the pyrroline-5-carboxylate metabolite i

SUBMITTER: Tran DH 

PROVIDER: S-EPMC9210447 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature