Hypoxia is more and more perceived as pivotal physiological driving force, allowing cells in the brain and elsewhere to acclimate to lowered oxygen (O(2)), and abridged metabolism. The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor-cognitive tasks, provoking a relative decrease in O(2) in relation to the acutely augmented requirement. We termed this fundamental, demand-dependent drop in O(2) availability “functional hypoxia.” Major players in …