Succinate-ubiquinone oxidoreductase (SDH)

Succinate-ubiquinone oxidoreductase, commonly referred to as Complex II or succinate dehydrogenase (SDH), is a vital enzyme complex situated in the inner mitochondrial membrane that functions in both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain (UniProt P31040). It catalyzes the oxidation of succinate to fumarate while simultaneously reducing ubiquinone to ubiquinol, facilitating electron flow without directly pumping protons across the membrane (Sun et al., 2005, Science). The complex is composed of four subunits (SDHA, SDHB, SDHC, and SDHD) and utilizes various cofactors including FAD and iron-sulfur clusters to transfer electrons (StatPearls, 2023). Clinically, SDH is recognized as a tumor suppressor; loss-of-function mutations lead to the accumulation of succinate, an oncometabolite that inhibits prolyl hydroxylases, resulting in the stabilization of hypoxia-inducible factors (HIF) and promoting tumorigenesis in conditions like hereditary paraganglioma (Gottlieb & Tomlinson, 2005, Nature Reviews Cancer). While traditionally a target for agricultural fungicides, it is an emerging therapeutic target in human medicine for treating ischemia-reperfusion injury and specific metabolic-dependent cancers (PubChem, 2024; PubMed 28551562).

Other names

Complex IISuccinate dehydrogenaseSuccinate:ubiquinone reductaseSQRSuccinate-Coenzyme Q reductase

Competitive inhibition of the succinate-binding site (S-site) or the ubiquinone-binding pocket (Q-site) to disrupt electron transfer and metabolic flux.