Essentiality of Succinate Dehydrogenase in Mycobacterium smegmatis and Its Role in the Generation of the Membrane Potential Under Hypoxia

Abstract

Complex II or succinate dehydrogenase (Sdh) is a major respiratory enzyme that couples the oxidation of succinate to fumarate in the cytoplasm to the reduction of quinone to quinol in the membrane. Mycobacterial species harbor genes for two putative sdh operons, sdh1 and sdh2, but the individual roles of these two operons are unknown. In this communication, we show that sdh1 and sdh2 are differentially expressed in response to energy limitation, oxygen tension, and alternative electron acceptor availability, suggesting distinct functional cellular roles. Sdh2 was essential for growth and generation of the membrane potential in hypoxic cells. Given the essentiality of succinate dehydrogenase and oxidative phosphorylation in the growth cycle of Mycobacterium tuberculosis, the potential exists to develop new antituberculosis agents against the mycobacterial succinate dehydrogenase. This enzyme has been proposed as a potential target for the development of new chemotherapeutic agents against intracellular parasites and mitochondrion-associated disease.