Succinate dehydrogenase complex iron sulfur subunit B (SDHB)

Succinate dehydrogenase subunit B (SDHB) is a nuclear-encoded protein that serves as the iron-sulfur subunit of mitochondrial Complex II, also known as succinate dehydrogenase (SDH) (UniProt: P21912). It plays a critical dual role in cellular metabolism, participating in the tricarboxylic acid (TCA) cycle by catalyzing the oxidation of succinate to fumarate and in the electron transport chain by transferring electrons to the ubiquinone pool (PubMed: 26925370). SDHB contains three iron-sulfur clusters ([2Fe-2S], [4Fe-4S], and [3Fe-4S]) that are essential for its electron-tunneling function (PubMed: 27604842). Mutations in the SDHB gene are a major cause of hereditary paraganglioma-pheochromocytoma syndrome and are also linked to gastrointestinal stromal tumors and renal cell carcinomas (NIH: MedlinePlus). The loss of SDHB function leads to the accumulation of succinate, which acts as an oncometabolite by inhibiting alpha-ketoglutarate-dependent dioxygenases and stabilizing hypoxia-inducible factor 1-alpha (HIF-1α) (PubMed: 25972245). This metabolic reprogramming promotes tumorigenesis, angiogenesis, and a shift toward glycolysis (Oncotarget: 2017). While primarily studied in the context of genetic deficiency, SDHB is also a target for specific inhibitors like malonate and atpenins, which are used in research and potentially for treating ischemia-reperfusion injury (PNAS: 2003).

Other names

Iron-sulfur subunit of complex IIIpSDH1SDH2PGL4CWS2MC2DN4PPGL4Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial

Inhibition of the succinate-ubiquinone reductase activity by competitive binding at the succinate site or the ubiquinone-binding site, thereby disrupting the TCA cycle and electron transport chain (PNAS: 2003, PubMed: 26925370).