Mycobacterial respiratory chain (MRC) (MRC)

The mycobacterial respiratory chain is a complex assembly of membrane-bound enzymes and electron carriers that facilitate oxidative phosphorylation to generate ATP, the primary energy currency of the cell [Cook et al., 2014, Microbiology Spectrum]. In Mycobacterium tuberculosis, this system is uniquely flexible, allowing the pathogen to adapt to varying oxygen levels and nutrient availability during different stages of infection, including dormancy [Hards et al., 2020, Frontiers in Microbiology]. Key components of this system include the NADH dehydrogenases (Ndh-1 and Ndh-2), the menaquinone pool, the cytochrome bc1-aa3 oxidase complex, and the F1F0-ATP synthase [Bald et al., 2017, Nature Communications]. Because mycobacteria lack the metabolic plasticity of many other bacteria, they are highly dependent on this respiratory apparatus for survival, making it an ideal target for therapeutic intervention [Beites et al., 2019, Cell Chemical Biology]. Drugs like Bedaquiline specifically target the ATP synthase to deplete energy reserves, while Telacebec (Q203) inhibits the cytochrome bc1 complex, effectively halting the electron transport chain [Andries et al., 2005, Science; Pethe et al., 2013, Nature Medicine]. Targeting these energetics has proven highly effective against multi-drug resistant strains of tuberculosis, though concerns regarding cardiotoxicity and drug-drug interactions remain significant clinical challenges [Mahajan, 2013, Int J Appl Basic Med Res].

Other names

Mycobacterial oxidative phosphorylation systemMycobacterial respiratory membrane/energetics systemMycobacterial electron transport chainMycobacterial energetics system

Inhibition of ATP synthase, inhibition of the cytochrome bc1-aa3 complex, and disruption of the proton motive force.