Succinate dehydrogenase-deficient gastrointestinal stromal tumors

Figure 3 Role of succinate dehydrogenase deficiency in the tumorigenesis of succinate dehydrogenase-deficient gastrointestinal stromal tumors. SDH complex dysfunction within mitochondria leads to increased levels of succinate, which in turn inhibits PHD activity. Non-hydroxylated HIF1α is resistant to VHL-mediated targeting for degradation and stimulates transcription of VEGF and IGF. SDH: Succinate dehydrogenase; HIF1α: Hypoxia-inducible factor α; PHD: Prolyl hydroxylase; E3 complex: Ubiquitin ligase complex; VHL: Von Hippel-Lindau; VEGF: Vascular endothelial growth factor; IGF: Insulin-like growth factor; PI3K: Phosphatidylinositol 3-kinase; mTOR: Mammalian target of rapamycin.