Schematic diagram of tumorigenesis in succinate dehydrogenase (SDH) and fumarate hydratase (FH). SDH and FH deficiency causes accumulation of succinate and fumarate, respectively, inside the mitochondria. These will be subsequently transported into the cytosol. High levels of succinate and fumarate can inhibit prolyl hydroxylases (PDH1-3), which plays a role in the degradation of HIF-1α under normoxic conditions. HIF-1α, when stabilized, induces transcription of nuclear genes involved in tumor suppression. αKG, α-ketoglutarate; ICT, isocitrate; CT, citrate; SCoA, Succinyl-coA; HIF, hypoxia-inducible factor Adapted from Zanssen S, Schon EA (2005) [49] and Shuch, B., Linehan, W.M., & Srinivasan, R. (2013) [50].