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Fig. 3. Modulation of oxygen sensor sensitivity by cofactors. Oxygen-sensing systems connecting an oxygen-dependent enzymatic activity to the regulation of hypoxia-inducible responses should operate at high and low PO2 affinities, fitting the heterogeneous PO2 distribution curve. Oxygen-sensing heme proteins such as mitochondrial complex IV (cytochrome c oxidase) and NAD(P)H-oxidase as well as PHD have been described as candidate sensor systems functioning at different Km values. Modulation of the specific PO2 affinities or oxygen sensor activities would allow efficient triggering and fine-tuning of various signal cascades to optimize cellular function and adaptation over a broad range of O2 concentrations.





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