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Peter Ratcliffe, Norma Masson, Tom Keeley and colleagues show that animal cells have an enzymatic oxygen sensor similar to one used in plants, opening routes for new therapeutic targets.

Sensing and responding to low oxygen levels (hypoxia) is essential for most cells and organisms, and dissecting oxygen sensing mechanisms is crucial for understanding and treating diseases that involve hypoxia, such as cancer and heart disease. The hypoxia-inducible factors (HIFs) – also co-discovered by Peter Ratcliffe – have been the only known oxygen sensors in animals. Now, in a paper published in Science, the Ludwig scientists and their collaborators show that a human enzyme called ADO senses oxygen levels via a mechanism involving splitting molecular oxygen and tagging target proteins for destruction. ADO has conserved counterparts in plants and it is likely to provide more rapid responses to hypoxia than HIF. This discovery also provides new avenues to investigate adaptive responses to hypoxia, with possibilities for therapeutic intervention.