Type 2 NADH:quinone oxidoreductase (NDH-2) (NDH-2)

Type 2 NADH:quinone oxidoreductase (NDH-2) is a membrane-bound respiratory enzyme that facilitates the transfer of electrons from NADH to the quinone pool, such as menaquinone or ubiquinone (UniProt: P9WIV3). Unlike the complex Type 1 NADH dehydrogenase (Complex I) found in the human mitochondria, NDH-2 is a single-polypeptide flavoenzyme that does not pump protons across the membrane, making it non-electrogenic (PubMed: 24478299). It is essential for maintaining the intracellular NAD+/NADH ratio and supporting the electron transport chain in various pathogens, including Mycobacterium tuberculosis and Plasmodium falciparum (PubMed: 17603103). Because humans lack this specific enzyme, NDH-2 is considered a high-priority target for the development of selective antimicrobial and antimalarial drugs. Inhibitors such as phenothiazines and quinolinone derivatives bind to the enzyme, disrupting the respiratory chain and leading to a lethal depletion of ATP and loss of redox balance (PubMed: 16418434). Consequently, targeting NDH-2 offers a promising strategy for overcoming drug resistance in infectious diseases.

Other names

NADH dehydrogenase (quinone)NDH-IINon-electrogenic NADH dehydrogenaseNADH:ubiquinone oxidoreductase (non-electrogenic)ndh

Inhibition of the transfer of electrons from NADH to the quinone pool, leading to the disruption of the respiratory chain, depletion of cellular ATP, and loss of redox homeostasis in pathogens.