Succinate dehydrogenase [ubiquinone] iron-sulfur subunit (SDHB)

The Succinate dehydrogenase [ubiquinone] iron-sulfur subunit (SDHB) is a nuclear-encoded component of the mitochondrial respiratory chain complex II, which serves as a vital link between the citric acid cycle and the electron transport chain. It functions by facilitating the transfer of electrons from succinate-derived FADH2 to ubiquinone through its three distinct iron-sulfur clusters (UniProt: P21912). Beyond its fundamental role in energy production, SDHB is recognized as a potent tumor suppressor; germline mutations in this subunit are a primary cause of hereditary paraganglioma-pheochromocytoma syndromes (PubMed: 11823443). Loss of SDHB function leads to the pathological accumulation of succinate, an oncometabolite that inhibits alpha-ketoglutarate-dependent dioxygenases, thereby promoting angiogenesis and epigenetic dysregulation (PubMed: 15660115). In the pharmaceutical context, while SDHB is a major target for agricultural fungicides known as SDHIs, it is increasingly investigated in human medicine as a biomarker for SDH-deficient cancers, including specific subtypes of gastrointestinal stromal tumors and renal cell carcinomas (PubMed: 21893128). Therapeutic strategies currently focus on exploiting the metabolic dependencies created by SDHB deficiency or identifying small molecules that can modulate mitochondrial respiration in metabolic diseases (PubMed: 28605213).

Other names

Succinate dehydrogenase complex subunit BIron-sulfur subunit of complex IISDH2SDHIPCWS2PGL4

Inhibition of the succinate binding site or the ubiquinone binding site within the mitochondrial respiratory chain complex II, preventing electron transfer and succinate oxidation.