Fig. 2.

HIF degradation pathway in normoxia and its stabilisation in hypoxia and pseudohypoxia. Under normoxic oxygen levels, PHD enzymes hydroxylate HIFα subunit on specific proline residues. These are recognised by VHL ubiquitin ligase which targets HIFα for proteasomal degradation (first panel). Under conditions of low oxygen levels, PHD enzymes are inhibited and HIFα protein is stabilised, binds HIFβ subunit and transactivates HIF responsive genes (middle panel). In pseudohypoxic conditions depicted here by SDH deficiency, high succinate levels restrict the PHD reaction by product inhibition and HIFα is stabilised under conditions of normoxic oxygen levels (last panel)