<i>Leishmania</i> type II dehydrogenase is essential for parasite viability irrespective of the presence of an active complex I
Margarida Duarte, Cleide E. Ferreira, Gurleen Kaur Khandpur, Tamara Flohr, Jannik Zimmermann, Helena Castro, Johannes M. Herrmann, Bruce Morgan, Ana M. Tomás
Abstract
Significance Leishmaniasis is one of the most dangerous, neglected tropical diseases. Oxidative phosphorylation is a known target of antipathogenic therapeutics. Herein, we addressed the contribution of type II NADH dehydrogenase (NDH2) and complex I activities to Leishmania physiology. Our results provide evidence that Leishmania NDH2 is essential throughout the parasites’ life cycle, independently of the presence of a functional complex I. Furthermore, sustained expression of NDH2 renders complex I dispensable. This indicates that NDH2 has unique and essential function(s) in Leishmania parasites and validates the enzyme as a promising drug target. Future studies may benefit from the Leishmania model to unravel the metabolic advantage of type II NADH dehydrogenases, enlightening the reason for their persistence across evolution.