subunitsSDHA

SDHA is the flavoprotein subunit of mitochondrial Complex II, also known as succinate dehydrogenase. It is a nuclear-encoded mitochondrial protein that forms the catalytic core of the complex, linking the citric acid cycle to the electron transport chain. The SDHA gene is located on chromosome 5p15.33 and is expressed in many tissues. The protein is imported into mitochondria where it binds a flavin adenine dinucleotide (FAD) prosthetic group required for its redox activity.

Functionally, SDHA catalyzes the oxidation of succinate to fumarate. In the process, electrons are transferred from succinate to FAD, forming FADH2, and then through the SDHB iron–sulfur protein to ubiquinone, reducing it to ubiquinol. This electron transfer feeds the ubiquinone pool of the respiratory chain but does not directly pump protons across the membrane. SDHA works in concert with the other subunits of Complex II to complete the catalytic cycle.

Complex II comprises four subunits: SDHA (flavoprotein catalytic subunit), SDHB (iron–sulfur protein with multiple Fe–S centers), and the membrane-anchoring subunits SDHC and SDHD, which contribute to the ubiquinone-binding site. The complex participates in both the TCA cycle and oxidative phosphorylation via ubiquinone reduction, linking metabolism to electron transport.

Genetics and disease: SDHA is ubiquitously expressed and imported into mitochondria. Pathogenic variants can cause complex II deficiency and mitochondrial disease. Germline SDHA mutations are associated with hereditary paraganglioma and pheochromocytoma syndromes, with tumors arising in various tissues. SDHA dysfunction can also contribute to metabolic and proliferative abnormalities observed in some cancers.

See also: succinate dehydrogenase, mitochondrial disease, paraganglioma.