is the catalytic subunit of succinate dehydrogenase (SDH) complex II of the mitochondrial electron transport chain. Complex II contains four subunits: the flavoprotein catalytic subunit SDHA, iron-sulfur protein SDHB, and a cytochrome b560 composed of SDHC and SDHD. Interaction with SDH5 is required for FAD attachment. Responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). Defects in SDHA cause defective mitochondrial oxidative phosphorylation, giving rise to heterogeneous clinical symptoms ranging from isolated organ dysfunction to multisystem disorder. Acetylation of SDHA may control entry of the substrate into the active site, thus regulating its enzymatic activity. Acetylated SDHA may be a SIRT3 substrate SIRT3 is a mitochondrial NAD(+)-dependent deacetylase. Increased succinate levels as a consequence of SDH deficiency inhibit hypoxia inducible factor-1alpha (HIF-1alpha) prolyl hydroxylases leading to sustained HIF-1alpha expression in tumours. Defects in SDHA cause of Leigh syndrome, a severe disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions. Note: This description may include information from UniProtKB.
Protein type: Mitochondrial; Oxidoreductase; EC 126.96.36.199; Carbohydrate Metabolism - citrate (TCA) cycle; Energy Metabolism - oxidative phosphorylation
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.