NADH dehydrogenase 2 (NDH-2)

NADH dehydrogenase 2 (NDH-2) is a membrane-bound respiratory enzyme that catalyzes the transfer of electrons from NADH to the ubiquinone pool (UniProt: P9WIA1). Unlike the mammalian Complex I (NDH-1), NDH-2 is a single-subunit flavoprotein that does not pump protons across the membrane to generate a proton motive force (PubMed: 23161311). It is found in various bacteria, fungi, and protozoa, including major human pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum (PubMed: 28438804). Because NDH-2 is absent in the human genome, it represents a highly attractive target for the development of selective antimicrobial and antiprotozoal therapies (PubMed: 25104318). Inhibition of NDH-2 leads to a rapid depletion of intracellular ATP and an accumulation of NADH, ultimately resulting in metabolic collapse and pathogen death (Wikipedia: NADH dehydrogenase (quinone)). Current research focuses on identifying small-molecule inhibitors, such as phenothiazine derivatives and quinolone-based compounds, to combat drug-resistant infections like tuberculosis and malaria (PubMed: 28438804).

Other names

Type II NADH:ubiquinone oxidoreductaseAlternative NADH dehydrogenaseNDH2NDH-IINADH:ubiquinone oxidoreductase (non-electrogenic)

Inhibition of the NADH oxidation and ubiquinone reduction sites within the respiratory chain, leading to ATP depletion and redox imbalance.