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. Author manuscript; available in PMC: 2020 Sep 3.
Published in final edited form as: Endocr Pract. 2017 Mar 23;23(6):690–704. doi: 10.4158/EP161718.RA

Fig. 3.

Fig. 3.

Involvement of the hypoxia-inducible factor (HIF) signaling pathway and tricarboxylic acid (TCA) cycle substrates in determining the noradrenergic phenotype of the tumor. Mutations in genes encoding HIF-α, tumor suppressor von Hippel-Lindau (pVHL), succinate dehydrogenase (SDH), fumarate hydratase (FH), and malate dehydrogenase (MDH)2 lead to stabilization of HIF-α. TCA cycle substrate accumulation hypermethylates the promoter region of phenylethanolamine N-methyltransferase (PNMT) and decreases its expression. *Genes encoding these proteins are implicated in pheochromocytoma and paraganglioma pathogenesis. ACO = aconitase; CS = citrate synthase; IDH = isocitrate dehydrogenase; KGDH = ketoglutarate dehydrogenase; succinyl-CoA = succinyl coenzyme A; SUCLG = succinyl-CoA synthetase.