Succinate dehydrogenase ubiquinone binding site (SDH Q-site)

The Succinate dehydrogenase (Complex II) ubiquinone binding site, often referred to as the Q-site, is a critical functional domain located at the interface of the SDHB, SDHC, and SDHD subunits within the mitochondrial inner membrane [UniProt: P21912, Q99643, O14521]. It serves as the catalytic center where electrons derived from the oxidation of succinate to fumarate are transferred from the terminal [3Fe-4S] cluster to ubiquinone, reducing it to ubiquinol [PMID: 28603041]. This site is unique because Complex II is the only enzyme that participates in both the tricarboxylic acid (TCA) cycle and the electron transport chain [StatPearls: NBK545253]. Pharmacologically, the Q-site is the primary target for a broad class of fungicides known as Succinate Dehydrogenase Inhibitors (SDHIs), such as Boscalid and Fluopyram [PMID: 23514175]. In human health, it is a subject of intense study in oncology because mutations in the subunits forming this site lead to succinate accumulation, which acts as an oncometabolite driving tumorigenesis in paragangliomas and pheochromocytomas [PMID: 25159734]. Dysregulation or inhibition of this site can lead to significant mitochondrial dysfunction, increased production of reactive oxygen species (ROS), and metabolic reprogramming [PMID: 17452640].

Other names

Complex II ubiquinone binding siteSuccinate-ubiquinone oxidoreductase Q-siteSQR Q-siteMitochondrial complex II Q-pocketSuccinate dehydrogenase (ubiquinone) binding site

Inhibition of electron transfer from the terminal iron-sulfur cluster (3Fe-4S) of the SDHB subunit to the ubiquinone molecule within the mitochondrial inner membrane [PMID: 28603041].