The proton-translocating NADH-quinone oxido-reductase (complex I in mitochondria or NDH-1 in bacteria) is the first enzyme in the respiratory chain that links electron transfer from NADH to quinone with proton translocation across the membrane. NDH-1 is a minimal composition of complex I and is composed of 13-15 subunits, all of which have their homologues in the mitochondrial enzyme that contains at least 45 subunits. NDH-1 and complex I have a characteristic L-shaped form with two domains, a membrane domain embedded in the bacterial cytoplasmic membrane (or inner-mitochondrial membrane) and a peripheral domain protruding into the cytoplasm (mitochondrial matrix). The peripheral domain catalyzes the electron transfer from NADH to quinone, and harbors all the essential cofactors (FMN and 8-9 iron-sulfur clusters). The membrane domain is composed of 7 dissimilar subunits (NuoA, H, J, K, L, M and N), whose mitochondrial counterparts are involved in various diseases. This domain has no cofactors and is believed to participate in proton translocation and quinone binding. Utilizing facility of gene manipulation in Escherichia coli, membrane domain subunits have been characterized. It was found that at least a few conserved carboxyl residues located in transmembrane segments are essential for energy-transducing NADH-quinone reductase. We describe the present status of the research on the structure and function of hydrophobic domain subunits of NDH-1 in this mini-review.