Rhodoquinone reaction site of mitochondrial complex I, in parasitic helminth, Ascaris suum

AbstractThe components and organization of the respiratory chain in helminth mitochondria vary remarkably depending upon the stage of the life cycle. Mitochondrial complex I in the parasitic helminth Ascaris suum uses ubiquinone-9 (UQ9) and rhodoquinone-9 (RQ9) under aerobic and anaerobic conditions, respectively. In this study, we investigated structural features of the quinone reduction site of A. suum complex I using a series of quinazoline-type inhibitors and also by the kinetic analysis of rhodoquinone-2 (RQ2) and ubiquinone-2 (UQ2) reduction. Structure–activity profiles of the inhibition by quinazolines were comparable, but not completely identical, between NADH-RQ2 and NADH-UQ2 oxidoreductase activities. However, the inhibitory mechanism of quinazolines was competitive and partially competitive against RQ2 and UQ2, respectively. The pH profiles of both activities differed remarkably; NADH-RQ2 oxidoreductase activity showed an optimum pH at 7.6, whereas NADH-UQ2 oxidoreductase activity showed two optima pH at 6.4 and 7.2. Our results indicate that although A. suum complex I uses both RQ2 and UQ2 as an electron acceptor, the manner of reaction (or binding) of the two quinones differs