Bacterial NADH:ubiquinone oxidoreductase (NDH)

Bacterial NADH dehydrogenase is a critical enzyme in the bacterial respiratory chain, responsible for the oxidation of NADH and the subsequent transfer of electrons to the quinone pool [UniProt]. In many bacteria, this process is mediated by two distinct enzymes: the proton-pumping NDH-1, which is homologous to mitochondrial Complex I, and the non-proton-pumping NDH-2 [PubMed: 21610066]. Because NDH-2 is absent in mammalian mitochondria, it represents a highly selective target for antimicrobial development, particularly against pathogens like Mycobacterium tuberculosis [PubMed: 15870197]. Inhibition of these enzymes disrupts the electrochemical gradient across the bacterial membrane, leading to a depletion of ATP and eventual cell death [Journal of Biological Chemistry, 2011]. Furthermore, certain drugs targeting NDH-2, such as clofazimine, can trigger the production of lethal levels of reactive oxygen species within the pathogen [PNAS, 2005]. By targeting these metabolic hubs, new therapeutic strategies aim to overcome existing antibiotic resistance mechanisms in chronic infections.

Other names

NADH dehydrogenaseComplex I (bacterial)NDH-1NDH-2Type II NADH dehydrogenaseNADH:quinone oxidoreductase

Inhibition of electron transfer from NADH to ubiquinone, leading to the disruption of the proton motive force and the induction of lethal reactive oxygen species (ROS) production [PubMed: 21610066, PNAS, 2005].