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 Q2 (Km ~ 12 μM), are competitively inhibited by menaquinone (Ki ~ 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". This article is protected by copyright. All rights reserved.