Anyone who has undertaken strenuous exercise, tried to hold their breath at the bottom of a swimming pool or climbed high mountain peaks will stress the importance of getting enough oxygen. This is also true for insects, although perhaps they admit their cravings for air somewhat less openly. Regardless,biologists have long appreciated the fact that insects have remarkable tolerance to low oxygen levels. But how is it possible for a fruit-fly to survive a lack of oxygen for hours when humans can barely endure several minutes? This is especially mystifying when considering flies' relatively high rates of resting energy consumption associated with their flight ability.

Jacob Feala, at the University of California, and colleagues from the Burnham Institute for Medical Research, San Diego, explored the energy pathways that Drosophila use during several hours of oxygen deprivation, or hypoxia, in order to better understand any potential metabolic advantage that these flies may have. First, the team employed nuclear magnetic resonance (NMR) spectroscopy to describe the changes in metabolic pathway end-products during hypoxia. The key by-products of energy metabolism found during these experiments were lactate, alanine and acetate. Obtaining high lactate concentrations was not particularly surprising, since this is the most common by-product of ATP production during oxygen shortage in mammals. However, discovering alanine and acetate was a little more unusual.

But the end-products of biochemical reactions do not fully explain what happens during hypoxia, especially if one is interested in knowing which pathways are employed. So, using the NMR results, and armed with the knowledge that most biochemical energy reactions in insects start with glycogen,trehalose and proline breakdown, the team subsequently built a model of all the potential ATP-producing pathways that might yield these mystery metabolites. Specifically, Feala's group included several pathways that produce alanine and acetate in order to find optimal production pathways for each of the biochemical compounds recorded during the NMR trials. To provide a simplified analogy, this process is like trying to work out the route that someone might have travelled on a large, complex railway system while the only information available is the starting station and end destination. Finally,using the refined information-based model, the team explored hypoxia adaptation by computer simulations of different energy and oxygen conditions.

Many hours of number-crunching revealed that the ability of the flies to produce these three biochemical end-products – alanine, acetate and lactate – could help them survive low oxygen by improving ATP production and the efficiency of glucose consumption, and also reducing proton production, which can lead to damaging pH fluctuations. It seems, therefore,that having more options for fermentation of an energy source contributes to the hypoxia tolerance of these flies. So do you want to hold your breath underwater for several hours? Well, Feala and co-workers have shown that all you need to do is take a deep breath and re-direct your anaerobic biochemical pathways to produce lactate, alanine and acetate instead of only lactate as you typically do when you run out of air.

Feala, J. D., Coquin, L., McCulloch, A. D. and Paternostro,G. (
). Flexibility in energy metabolism supports hypoxia tolerance in Drosophila flight muscle: metabolomic and computational systems analysis.
Mol. Syst. Biol.