Mycobacterial menaquinone-dependent respiratory chain (Mycobacterial ETC)

The mycobacterial menaquinone-dependent respiratory chain is a vital metabolic pathway in Mycobacterium tuberculosis (Mtb) responsible for generating the proton motive force (PMF) required for ATP synthesis and maintaining redox balance (Cook et al., 2014, PMID: 24511371). This system is unique because it utilizes menaquinone (MK-9) as the sole lipophilic electron carrier, whereas mammalian cells use ubiquinone (Hards et al., 2020, PMID: 32661241). The chain consists of various electron donors like NADH dehydrogenase 2 (NDH-2) and terminal oxidases such as the cytochrome bcc-aa3 supercomplex and cytochrome bd oxidase (Bald et al., 2017, PMID: 28341641). Targeting this pathway has proven highly effective in treating multi-drug resistant tuberculosis, as evidenced by the clinical success of bedaquiline, which inhibits the F1Fo-ATP synthase (Andries et al., 2005, PMID: 15647434). Other novel agents like telacebec (Q203) target the QcrB subunit of the cytochrome bcc complex, further validating the respiratory chain as a cornerstone for modern anti-mycobacterial drug discovery (Pethe et al., 2013, PMID: 23913001).

Other names

Mycobacterial electron transport chainMycobacterial oxidative phosphorylation systemM. tuberculosis respiratory chain

Inhibition of ATP synthase, inhibition of the cytochrome bcc complex (QcrB), and disruption of the proton motive force through electron transport interference.