Synthetic lethality of Mycobacterium tuberculosis NADH dehydrogenases is due to impaired NADH oxidation.

ABSTRACT: Type 2 NADH dehydrogenase (Ndh-2) is an oxidative phosphorylation enzyme discussed as a promising drug target in different pathogens, including Plasmodium falciparum and Mycobacterium tuberculosis (Mtb). To kill Mtb, Ndh-2 needs to be inactivated together with the alternative enzyme type 1 NADH dehydrogenase (Ndh-1), but the mechanism of this synthetic lethality remained unknown. Here, we provide insights into the biology of NADH dehydrogenases and a mechanistic explanation for Ndh-1 and Ndh-2 synthetic lethality in Mtb. NADH dehydrogenases have two main functions: maintaining an appropriate NADH/NAD+ ratio by converting NADH into NAD+ and providing electrons to the respiratory chain. Heterologous expression of a water forming NADH oxidase (Nox), which ca

SUBMITTER: Xu Y 

PROVIDER: S-EPMC10120654 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature