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Succinate dehydrogenase complex subunit A (SDHA)
- Target
- SDHA
- Molecular classification
- Enzyme, Mitochondrial respiratory chain complex II component
01
Overview
Succinate dehydrogenase complex subunit A (SDHA) is the major catalytic subunit of succinate dehydrogenase (complex II) in the mitochondrial inner membrane. It oxidizes succinate to fumarate in the citric acid cycle and transfers electrons via FAD to the respiratory chain, linking cellular metabolism and ATP generation. SDHA is essential for energy production in all aerobic cells. It acts as a tumor suppressor: mutations or loss of function can cause mitochondrial diseases such as Leigh syndrome and predispose to certain cancers (e.g., paraganglioma, gastrointestinal stromal tumors). Experimental small-molecule inhibitors target SDHA in research and agriculture, but broad inhibition is toxic due to disruption of cellular energy metabolism[1][4][7].
- Other names
- succinate dehydrogenase complex, subunit A, flavoproteinsuccinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrialSDH1SDH2SDHFflavoprotein subunit of complex IIFPCMD1GGDHSA_HUMANsuccinate dehydrogenase complex flavoprotein subunit[4][1][7]
02
Mechanism of action
Inhibition of SDHA reduces conversion of succinate to fumarate, disrupting the citric acid cycle and electron transport, leading to reduced ATP production and potential induction of cell death in susceptible cells
03
Biological functions
Energy metabolismCitric acid cycle (Krebs cycle)Oxidative phosphorylationElectron transportOxygen sensing
04
Disease associations
CancerNeurodegenerative diseaseCardiovascular diseaseMitochondrial disease (including Leigh syndrome, paraganglioma, gastrointestinal stromal tumor)[1][4][7]
05
Safety considerations
Systemic inhibition can cause mitochondrial dysfunction, lactic acidosis, encephalopathy, and multi-organ toxicityGermline mutations linked to tumorigenesis (cancer predisposition), especially paraganglioma and gastrointestinal stromal tumorLoss-of-function mutations cause severe mitochondrial disorders (e.g., Leigh syndrome)[4]
06
Interacting drugs
Atpenin A5 (experimental SDH inhibitor; not clinically approved)
3 more in the full profile.
07
Biomarkers
SDHA mutation or immunohistochemistry (IHC) loss used as a biomarker in paraganglioma, pheochromocytoma, and mitochondrial disordersSDHA protein loss as a diagnostic marker for SDH-deficient tumors[4]
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