Succinate dehydrogenase ubiquinone-binding site (SDH Q-site)

Mitochondrial Complex II, or succinate dehydrogenase (SDH), is a heterotetrameric enzyme that functions in both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain (Sun et al., 2005, Science). The Q-binding site is a critical hydrophobic pocket formed by the SDHB, SDHC, and SDHD subunits, where ubiquinone (Coenzyme Q) is reduced to ubiquinol (Yankovskaya et al., 2003, Science). This site facilitates the transfer of electrons from FADH2, through a series of iron-sulfur clusters, to the quinone pool. Mutations in the genes encoding the Q-site subunits are linked to the development of pheochromocytomas and paragangliomas, as the resulting loss of SDH activity leads to the accumulation of succinate, a known oncometabolite (Selak et al., 2005, Nature). Pharmacologically, the Q-site is the primary target for succinate dehydrogenase inhibitor (SDHI) fungicides, such as boscalid and fluopyram, which are used extensively in agriculture (Sierotzki & Scalliet, 2013, Phytopathology). In a clinical context, targeting this site is being explored to manage oxidative stress during ischemia-reperfusion injury and to induce apoptosis in specific cancer cells via the production of reactive oxygen species (ROS) (Kluckova et al., 2013, ISRN Oxidative Medicine).

Other names

Complex II Q-binding siteSuccinate-ubiquinone oxidoreductase Q-pocketSDH ubiquinone-binding siteMitochondrial Complex II Q-siteUbiquinone-binding site of Succinate dehydrogenase

The mechanism involves the competitive or non-competitive binding of molecules within the ubiquinone-binding pocket, which prevents the docking of ubiquinone and halts the transfer of electrons from the iron-sulfur clusters of the SDHB subunit (Cecchini, 2003, Annual Review of Biochemistry).