Mitochondrial NADP(H) generation is essential for proline biosynthesis.
basic_science · Level V
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- Record sourced from PubMed, PMID 33888598.
- Also identified by DOI 10.1126/science.abd5491 and PMC identifier 8241437.
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Abstract
The coenzyme nicotinamide adenine dinucleotide phosphate (NADP<sup>+</sup>) 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 <i>NADK2</i> 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.
Medical subject headings
- Mitochondria
- Mitochondrial Proteins
- NADP
- Phosphotransferases (Alcohol Group Acceptor)
- Proline