Current paradigms in cellular oxygen sensing.

Organisms, tissues and cells react to hypoxia by activating adaptive responses that tend to preserve systemic oxygen transport, cellular oxygen delivery, and the resistance of cells against the consequences of severe hypoxia. These responses are required for embryonic development and for survival through adulthood. Although much has been learned about the signaling pathways that are activated in hypoxic cells, the underlying mechanism of O2 sensing is not established. Most of the putative models of O2 sensing include the involvement of redox-dependent reactions and many implicate reactive oxygen species in the signaling process. The sources of these oxidant signals are thought to include members of the NAD(P)H oxidase system and/or mitochondria. This article reviews evidence for and against the involvement of these systems in the O2 sensing pathway.