**2. Main Components of the OxPhos Pathway in** *M. tb*

The ETC of *M. tb* comprises nine primary dehydrogenases, which fuel the respiratory chain as electron donors, and four-terminal oxidoreductases, which catalyse the transfer of electrons to terminal electron acceptors such as oxygen [14]. The lipoquinone, menaquinone (MK), serves as the intermediary electron carrier between the primary dehydrogenases and terminal oxidoreductases. In the following section, we summarise the main components of the pathway against which inhibitors have been discovered and those which are potentially suitable drug targets. In particular, this includes the NADH dehydrogenases, succinate dehydrogenase, the MK biosynthesis pathway, the two terminal oxidases, ATP synthase and the PMF (Figure 1).

**Figure 1.** Schematic representation of the *Mycobacterium tuberculosis* (*M. tb*) electron transport chain (ETC) and menaquinone (MK) biosynthesis pathway. Electrons provided by NADH are fuelled to the ETC by the NADH dehydrogenases (mainly NDH-2 in *M. tb*), leading to the reduction of menaquinone (MKH2). MK is the sole carrier of electrons across the ETC and eight main enzymes are involved in its biosynthesis. The succinate dehydrogenases Sdh1 and Sdh2 also contribute to the reduction of the menaquinone pool. Electrons from the menaquinone pool are then transferred to one of the terminal oxidases, the proton-pumping Cyt-bcc-aa3 or the Cyt-bd oxidase, both of which catalyse the reduction of oxygen to water. Along the respiratory chain, protons are pumped across the membrane, which generate the proton motive force (PMF) that is then used by the F1F0 ATP synthase to produce ATP.
