Mycobacterial respiratory chain

The mycobacterial respiratory chain is a branched electron transport system critical for the energy metabolism of mycobacteria, including Mycobacterium tuberculosis. It is composed of multiple dehydrogenases that transfer electrons to a lipid-soluble carrier, menaquinone, which then delivers electrons through two main terminal oxidase branches: the cytochrome bc1-aa3 oxidoreductase supercomplex (also called bcc-aa3 or Complex III2IV2) and cytochrome bd oxidase. The bc1-aa3 supercomplex is essential for efficient ATP generation under aerobic conditions by coupling electron transfer to proton translocation, while cytochrome bd supports survival under stress or low-oxygen conditions. Both branches are now validated therapeutic targets, and inhibition of their activity has shown efficacy against drug-resistant and persistent tuberculosis. Several drug classes are in development that inhibit specific components, particularly QcrB in the bc1 complex, with compound classes such as Q203 and related molecules showing clinical potential. Combined inhibition of both terminal oxidase branches can result in bactericidal activity and rapid clearance of tuberculosis infection.

Other names

Mycobacterial electron transport chainMycobacterial ETCMycobacterial respiratory supercomplex (referring to bc1-aa3)Cytochrome bcc-aa3 oxidoreductase supercomplexCytochrome bd oxidase branch

Inhibition of ATP synthesis (e.g., Bedaquiline blocks ATP synthase); Inhibition of cytochrome bc1 (QcrB) (e.g., Q203, SCR0911, MTC420); Inhibition of cytochrome bd (e.g., Aurachin D); Inhibition of oxidative phosphorylation; Disruption of proton motive force