A key mechanism against oxygen deficiency discovered: it is shared by plants and humans and activates within the first 5 minutes

A single protein acts as a true “survival switch” when oxygen becomes scarce, and this mechanism is common to plants and animals, including humans. This is the discovery at the heart of an international study published in PNAS, involving the University of Pisa, the Sant’Anna School of Advanced Studies, and the University of Oxford. The research identified the molecular mechanism that is activated within the very first minutes of hypoxia, triggering the cellular defense response.

“We have shown that the initiation of the hypoxia response depends on a single molecular circuit based on one protein,” explains Beatrice Giuntoli, a professor in the Department of Biology at the University of Pisa and one of the study’s authors. “It works like a switch: in the first few minutes, cells detect the lack of oxygen and immediately activate their defenses.”

“What is most interesting is that this molecular ‘trigger’ is not exclusive to plants,” Giuntoli adds. “A very similar protein is also present in humans and participates in the mechanisms by which cells sense oxygen variations. It is not the only system in humans, but in some tissues it could play an important role, with very rapid timing similar to what we observe in plants.”

When oxygen levels decrease, the ability to respond quickly is crucial. In plants, this initial signal is mediated by a family of enzymes known as Plant Cysteine Oxidases (PCOs), which act as molecular sensors and activate the genes needed to adapt to stress. All other response mechanisms—already known—come into play only later, but it is this initial “trigger” that determines the effectiveness of the response. A similar mechanism also exists in humans: the enzyme ADO, a functional homolog of plant PCOs, contributes to oxygen sensing in tissues.

“The innovation of this research is also methodological,” Giuntoli continues. “To isolate and study this mechanism in its essential form, we used an innovative synthetic biology approach: we essentially ‘transplanted’ the molecular circuit from plants into yeast cells, an organism that does not naturally possess this system. This allowed us to directly observe the circuit’s behavior without interference and demonstrate that it alone is sufficient to initiate the hypoxia response.”

The experiment showed that the response is activated extremely rapidly—within about five minutes—confirming that the earliest moments are crucial for cellular survival. Only afterward do other mechanisms come into play, amplifying and stabilizing the response.

“In plants, oxygen deficiency is a frequent condition, for example during floods,” Giuntoli concludes. “In such contexts, the speed of the response can make the difference between survival and death.”