Cellular response against hypoxia, where the available oxygen becomes limited, is mainly regulated by the transcriptional factor hypoxia-inducible factor (HIF) and its negative regulator prolyl hydroxylase (HIF-PH or PHD).
Recently, five HIF-PH inhibitors, which can activate HIF-dependent hypoxic response, have been approved against renal anemia in Japan and have already been used in clinics.
However, inhibiting PHDs is not just activating HIF-dependent hypoxic response but also is involved in regulating cellular metabolism.
Here we show that PHD inhibition could regulate cellular metabolism both in HIF-dependent and independent manner. It‘d be appreciated if we could discuss repositioning HIF-PHD inhibitors to treat various diseases.