1. Nat. Rev. Nephrol. doi:10.1038/nrneph.2017.145
Figure 1 Hypoxia-inducible transcription factor regulation and its effect on neutrophil function
Figure 1 | Hypoxia-inducible transcription factor regulation and its effect on neutrophil function. a | In the presence of oxygen (upper panel; normoxia), hypoxia-inducible transcription factor-α (HIFα) is hydroxylated by prolyl hydroxylases (PHDs). The requirement of 2-oxoglutarate (2-OG) as a co-substrate and the yield of succinate as a by-product link HIF hydroxylation with the tricarboxylic acid (TCA) cycle. Hydroxylated HIF is targeted for proteasomal degradation. In the absence of oxygen, under conditions of PHD inhibition and in models of PHD depletion (lower panel), un-hydroxylated HIF escapes degradation and activates HIF-responsive target genes. b | Deletion of PHD2 in neutrophils tips the balance between activation and deactivation (with reduced deactivation indicated by the dashed line) and thereby promotes and sustains neutrophil responses to pathogens.
Eckardt, K.-U. (2017) Oxygen sensing and cell metabolism in inflammation
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