Searching for molecular hypoxia sensors among oxygen-dependent enzymes.

Li, Li; Shen, Susan; Bickler, Philip; Jacobson, Matthew P; Wu, Lani F; Altschuler, Steven J · Elife · 2023

review · Level V

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Abstract

The ability to sense and respond to changes in cellular oxygen levels is critical for aerobic organisms and requires a molecular oxygen sensor. The prototypical sensor is the oxygen-dependent enzyme PHD: hypoxia inhibits its ability to hydroxylate the transcription factor HIF, causing HIF to accumulate and trigger the classic HIF-dependent hypoxia response. A small handful of other oxygen sensors are known, all of which are oxygen-dependent enzymes. However, hundreds of oxygen-dependent enzymes exist among aerobic organisms, raising the possibility that additional sensors remain to be discovered. This review summarizes known and potential hypoxia sensors among human O<sub>2</sub>-dependent enzymes and highlights their possible roles in hypoxia-related adaptation and diseases.

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