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

Type II NADH-quinone oxidoreductase (NDH-2) is a membrane-bound respiratory enzyme found in various bacteria, fungi, and protists, but notably absent in the human mitochondrial respiratory chain (Senn et al., 2015). It catalyzes the transfer of electrons from NADH to the quinone pool without the translocation of protons across the membrane, distinguishing it from the proton-pumping Type I NADH dehydrogenase (Complex I) (Heikal et al., 2014). Because humans rely exclusively on Complex I, NDH-2 represents a highly attractive target for the development of selective antimicrobial and antiparasitic agents (Cook et al., 2014). Inhibition of NDH-2 disrupts the respiratory chain, leading to a collapse of the membrane potential, depletion of cellular ATP, and an imbalance in the NADH/NAD+ ratio, ultimately resulting in cell death (Yano et al., 2011). This target is particularly relevant in the search for new treatments against Mycobacterium tuberculosis and Plasmodium falciparum, where it serves as a metabolic bottleneck (Eschemann et al., 2005).

Other names

NADH:ubiquinone oxidoreductase (non-electrogenic)Alternative NADH dehydrogenaseNDH-IINADH dehydrogenase type IINADH dehydrogenase (quinone)

Inhibition of the catalytic site responsible for electron transfer from NADH to the quinone pool, disrupting the respiratory chain and ATP production (Yano et al., 2011).