Searching for molecular hypoxia sensors among oxygen-dependent enzymes
Li Li, Susan Q. Shen, Philip E. Bickler, Matthew P. Jacobson, Lani F. Wu, Steven J. Altschuler
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 2 -dependent enzymes and highlights their possible roles in hypoxia-related adaptation and diseases.