Succinate dehydrogenase complex subunit D (SDHD)

Succinate dehydrogenase complex subunit D (SDHD) is an integral membrane protein that forms part of succinate dehydrogenase (complex II) in the mitochondrial inner membrane. It is one of four subunits (along with SDHA, SDHB, and SDHC) and functions as an anchor, ensuring the complex is properly situated in the membrane. SDHD cooperates with other subunits to transfer electrons from succinate (via FAD and Fe-S clusters) to ubiquinone, linking the citric acid cycle and the electron transport chain for ATP production. Mutations in the SDHD gene disrupt mitochondrial energy metabolism and are strongly implicated in certain familial cancers, including paragangliomas, pheochromocytomas, and gastrointestinal stromal tumors. Functional loss of SDHD impairs succinate conversion, stabilizes HIF, and promotes tumorigenesis through altered oxygen sensing and metabolic signaling[1][2][3][4][5][6].

Other names

SDHDsuccinate dehydrogenase [ubiquinone] cytochrome b small subunitsuccinate dehydrogenase cytochrome b560 subunitcomplex II subunit D

Inhibition of SDH (complex II) enzymatic activity blocks electron flow, leading to accumulation of succinate, altered cellular metabolism, and induction of cell death or differentiation depending on context Inhibition alters cellular redox state and can promote hypoxia-inducible factor (HIF) stabilization