Fig. 1.

SDH structure and its role in TCA cycle. a Assembly of four SDH subunits (SDHA-D) into functional SDH and its position in the mitochondrial inner membrane (IMM) facing matrix. The catalytic subunit SDHA contains the flavin cofactor FAD which accepts electrons from succinate and passes them to FeS centres in the SDHB subunit. The electrons are then accepted by membrane carrier ubiquinone (Q) at the Q binding site comprised by membrane embedded SDHC and SDHD subunits. Reduced Q (QH₂) transfers electrons within the IMM to complex III. b Enzymes of TCA cycle and accompanying replenishing reactions. CS citrate synthase, IDH isocitrate dehydrogenase, OGHD oxoglutarate dehydrogenase, SDH succinate dehydrogenase, FH fumarate hydratase, MDH malate dehydrogenase, PDH pyruvate dehydrogenase, PC pyruvate carboxylase, GOT glutamate-oxaloacetate transaminase, GLDH glutamate dehydrogenase. Enzymes with mutations found in PPGL are outlined in orange. Grey colour depicts pathways important in SDH deficiency (see text for details)