Oxygen sensing strategies in mammals and bacteria
#MMPMID24468676
Taabazuing CY
; Hangasky JA
; Knapp MJ
J Inorg Biochem
2014[Apr]; 133
(?): 63-72
PMID24468676
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The ability to sense and adapt to changes in pO2 is crucial for basic metabolism
in most organisms, leading to elaborate pathways for sensing hypoxia (low pO2).
This review focuses on the mechanisms utilized by mammals and bacteria to sense
hypoxia. While responses to acute hypoxia in mammalian tissues lead to altered
vascular tension, the molecular mechanism of signal transduction is not well
understood. In contrast, chronic hypoxia evokes cellular responses that lead to
transcriptional changes mediated by the hypoxia inducible factor (HIF), which is
directly controlled by post-translational hydroxylation of HIF by the non-heme
Fe(II)/?KG-dependent enzymes FIH and PHD2. Research on PHD2 and FIH is focused on
developing inhibitors and understanding the links between HIF binding and the O2
reaction in these enzymes. Sulfur speciation is a putative mechanism for acute
O2-sensing, with special focus on the role of H2S. This sulfur-centered model is
discussed, as are some of the directions for further refinement of this model. In
contrast to mammals, bacterial O2-sensing relies on protein cofactors that either
bind O2 or oxidatively decompose. The sensing modality for bacterial O2-sensors
is either via altered DNA binding affinity of the sensory protein, or else due to
the actions of a two-component signaling cascade. Emerging data suggests that
proteins containing a hemerythrin-domain, such as FBXL5, may serve to connect
iron sensing to O2-sensing in both bacteria and humans. As specific molecular
machinery becomes identified, these hypoxia sensing pathways present therapeutic
targets for diseases including ischemia, cancer, or bacterial infection.
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