Polyphosphate-dependent nicotinamide adenine dinucleotide (NAD) kinase: A novel missing link in human mitochondria

Polyphosphate [poly(P)] is described as a homopolymer of inorganic phosphates. Nicotinamide adenine dinucleotide kinase (NAD kinase) catalyzes the phosphorylation of NAD⁺ to NADP⁺ in the presence of ATP (ATP-NAD kinase). Novel NAD kinase that explicitly phosphorylates NAD⁺ to NADP⁺ using poly(P), besides ATP [ATP/poly(P)-NAD kinase], was found in bacteria, in particular, Gram-positive bacteria, and the gene encoding ATP/poly(P)-NAD kinase was also newly identified in Mycobacterium tuberculosis H37Rv. Both NAD kinases required multi-homopolymeric structures for activity expression. The enzymatic and genetic results, combined with their primary and tertiary structures, have led to the discovery of a long-awaited human mitochondrial NAD kinase. This discovery showed that the NAD kinase is a bacterial type of ATP/poly(P)-NAD kinase. These pioneering findings, i.e., ATP/poly(P)-NAD kinase, NAD kinase gene, and human mitochondrial NAD kinase, have significantly enhanced research on the biochemistry, molecular biology, and evolutionary biology of NAD kinase, mitochondria, and poly(P), including some biotechnological knowledge applicable to NADP⁺ production.