New insights into oxygen sensing at a cellular level

The ability of cells to detect and respond to a fall in oxygen tension is of fundamental importance for maintaining oxidative metabolism and tissue homeostasis. One of the challenges facing scientists working in this area has been that any proposed mechanism for oxygen sensing has to accommodate the very different tolerances of certain tissues to hypoxia and the extreme variation in the cellular responses observed. Hence, while skeletal muscle cells can recover function after 30 minutes of anoxia, the brain suffers irreparable damage after only 4–6 minutes of ischaemia.1 Moreover, while carotid body cells respond to changes in oxygen tension that barely register in non-chemosensory tissues (and do so within seconds),2 upregulation of erythropoietin synthesis in the interstitial peritubular cells is transcriptionally regulated and requires far more protracted periods of hypoxaemia.3 Despite such variances in oxygen sensitivity and response time, all cells appear capable of responding to hypoxia and the essential components of a universal oxygen sensing mechanism have at last begun to emerge. Moreover, from studies conducted in stroke and heart disease, it is apparent that therapeutic targeting of this novel pathway is set to transform our approach to pathology previously deemed intractable.