How Fruit Flies Deal with Radicals

Oxidative stress affects all living organisms, and the damage it causes is believed to play a part in cancer, diabetes, and Alzheimer’s, among other conditions. In a study published today in Immunity, EPFL researchers observed that, under acute oxidative stress, fruit flies remove and excrete damage-causing lipids from their blood.

Like humans, fruit flies produce molecules known as reactive oxygen species (ROS). Under normal circumstances, the harmful effects of ROS are counteracted by our cells’ natural defense mechanisms as well as antioxidants such as vitamins C and E. Yet stressors like pathogens, smoking, and ultraviolet light can upset the balance, sending ROS production into overdrive.

In their study, the researchers happened upon a previously unknown defense strategy against ROS after observing that mutant flies were dying a few days after exposure to a normally benign pathogen. “Because the flies were dropping fast, we decided to have a bit of fun,” says senior author Bruno Lemaitre. “We named the mutated gene and the protein after Marco Materazzi, the Italian soccer player on the receiving end of Zinedine Zidane’s infamous headbutt in the World Cup final.”

The reason for the fly deaths was that the mutation prevented the production of a fat-binding protein in the kidneys. “We were baffled by what we discovered,” Lemaitre explains. “Why were insects under pathogen-induced stress dying because they couldn’t produce a fat-binding protein in their kidneys?”

The answer was due to a secondary mechanism of oxidative stress, by which free radicals attack lipids in the blood, producing toxic compounds and even more ROS. This self-perpetuating process, known as lipid peroxidation, has to be brought under control at all costs.

Fruit flies have a simple yet effective way of stopping this process from spiraling out of control: they remove one part of the equation altogether. Certain stressors cause the fly’s kidneys to begin producing the Materazzi protein, which binds to the lipids in its blood. These are then passed out in the insect’s feces.

The scientists suspect this same mechanism could play an important role in other animals. Previous studies have identified an allergen in cockroach droppings that bears many similarities to the Materazzi protein. “Just like the flies in our study, all living organisms have to deal with oxidative stress damage,” Lemaitre adds. “I wouldn’t be surprised to see it become a major public health issue.”