Quinolone Signal molecule PQS behaves like a B Class inhibitor at the I site of mitochondrial complex I.

is a Gram-negative bacterium of the proteobacteria class, and one of the most common causes of nosocomial infections. For example, it causes chronic pneumonia in cystic fibrosis patients. Patient sputum contains 2-heptyl-4-hydroxyquinoline -oxide [HQNO] and quorum sensing molecules such as the quinolone signal [PQS]. It is known that HQNO inhibits the enzyme activity of mitochondrial and bacterial complex III at the Q (quinone reduction) site, but the target of PQS is not known. In this work we have shown that PQS has a negative effect on mitochondrial respiration in HeLa and A549 cells. It specifically inhibits the complex I of the respiratory chain. In vitro analyses showed a partially competitive inhibition with respect to ubiquinone at the I site. In competing studies with Rotenone, PQS suppressed the ROS-promoting effect of Rotenone, which is typical for a B-type inhibitor. Prolonged incubation with PQS also had an effect on the activity of complex III.