Alternative, nonproton pumping NADH:quinone oxidoreductase that delivers electrons to the respiratory chain by oxidation of NADH and reduction of quinones (PubMed:6784762, PubMed:7009604, PubMed:7020757, PubMed:6362717, PubMed:3122832, PubMed:2679883, PubMed:10664466). Utilizes NADH exclusively, and electron flow from NADH to ubiquinone does not generate an electrochemical gradient (PubMed:3122832, PubMed:2679883). It may also contribute to copper homeostasis and bacterial oxidative protection (PubMed:7487066, PubMed:10510271, PubMed:16759635, PubMed:21390523). Shows cupric reductase activity, and catalyzes the reduction of Cu(2+) to Cu(+) with NADH as electron donor (PubMed:10510271). Exhibits Cu(2+) reductase activity in the presence of either FAD or quinone, but is unable to reduce Fe(3+) (PubMed:10510271). Contains thiolate-bound copper (PubMed:12176061). a quinone + H(+) + NADH = a quinol + NAD(+) a ubiquinone + H(+) + NADH = a ubiquinol + NAD(+) H(+) + NADH + ubiquinone-8 = NAD(+) + ubiquinol-8 2 Cu(2+) + NADH = 2 Cu(+) + H(+) + NAD(+) Binds 1 FAD per subunit. Requires Mg2(+) for activity in vitro (PubMed:2679883). Inhibited by 3-n-dodecylmercapto-2-hydroxy-1,4-naphthoquinone (PubMed:7009604). The quinone-dependent Cu(2+) reduction is partially inhibited by superoxide dismutase (PubMed:10510271). Monomer (PubMed:7020757). Forms a supercomplex with the NADH:quinone oxidoreductase NDH-1 in the aerobic respiratory chain (PubMed:21040753). Membrane-bound (PubMed:10664466). Interaction with the membrane is probably mediated by amphipathic helices and electrostatic interactions (PubMed:15581635). Copurifies with phospholipids (PubMed:7020757, PubMed:6362717). Expression is subject to a complex network of regulatory controls at the transcriptional level (PubMed:8809757, PubMed:9168602). Under anaerobic conditions, is repressed by the global transcriptional regulator FNR, which binds at two sites in the ndh promoter region (PubMed:9168602). Transcription can be activated or repressed by the DNA-binding protein Fis (Nbp): at high concentrations, during early-exponential phase, Fis represses ndh transcription by binding to at least three sites in the ndb promoter, whereas at low concentrations Fis activates ndh expression by binding solely to the far upstream high-affinity site (PubMed:8809757). Also regulated by the integration host factor (IHF) and the histone-like protein HU (PubMed:9308170). Contains four structural/functional domains: the FAD-binding domain, the NAD(H)-binding domain, the copper-binding domain and the domain of anchorage to the membrane at the C-terminus. Disruption mutant retains membrane-bound NADH dehydrogenase activity and shows no obvious growth defects. Mutations at two sites, one in ndh and one in nuo locus, remove the NADH oxidase activity from E.coli membranes (PubMed:8387992). The ndh deficient strain is more sensitive than the wild-type to Cu(II)/tert-butyl hydroperoxide (t-BOOH). Furthermore, several ndh deficient mutants grew less well than the corresponding parental strains in media containing either high or low copper concentrations (PubMed:16759635). The Cu(II)-reduction rate of the cell decreases by about 10% in the absence of NDH-2 and by about 85% in a strain lacking both NDH-2 and quinones (PubMed:21390523). Activity in vitro is generally measured with ubiquinone-1 as the electron acceptor. The physiological electron acceptor is probably ubiquinone-8. Belongs to the NADH dehydrogenase family.