Circadian Clocks’ interactions with Oxygen Biology

In mammals, physiology and metabolism are shaped both by immediate and anticipatory responses to environmental changes through myriad of molecular mechanisms. While the former is mostly mediated through different acute signaling pathways the latter is primarily orchestrated by the circadian clock. Oxygen is vital for life and as such mammals have evolved different mechanisms to cope with changes in oxygen levels. It is widely accepted that oxygen sensing through HIF-1 signaling pathway is paramount for the acute response to changes in oxygen levels. Circadian clocks are molecular oscillators that control 24 h rhythms in various aspects of physiology and behavior. Evidence emerging in recent years from others and us points towards pervasive molecular and functional interactions between these two pathways on multiple levels. Specifically, we found that physiological daily oscillations in oxygen levels are circadian clock controlled and can reset the clock through HIF-1. Furthermore, we showed that the hypoxic response is tissue specific and day-time dependent. Finally, we obtained evidence for the interaction between these two pathways also in humans. I will present different aspects of our work on the crosstalk between the circadian clock and oxygen biology in mammals both under physiologic and pathologic conditions.