Alternate quinone coupling in a new class of succinate dehydrogenase may potentiate mycobacterial respiratory control.

There is a paucity of information on the unique components that pathogens use to form respiratory chains. It is not known why mycobacteria encode multiple succinate dehydrogenases (SDHs) to perform menaquinone-linked succinate oxidation, a thermodynamically unfavorable reaction (ΔG° = +21 kJ·mol ). In other bacteria, specific di-heme SDHs overcome this using the proton motive force. It is unknown if this holds true in mycobacteria. Here, succinate dehydrogenase 1 (Sdh1) from Mycobacterium smegmatis was purified and found to not contain heme cofactors. Proteoliposomes, containing Sdh1, are active with coenzyme Q (K  ~ 12 μm), are competitively inhibited by menaquinone (K  ~ 25 μm) and do not generate or consume electrochemical gradients. Sdh1 may use higher potential quinones in vivo and forms a novel SDH class, which we term 'Type F'.