Researchers at the University of Bath have found that skin cells from individuals with the rare genetic disorder Friedrich’s Ataxia are four to 10 times more likely to be damaged by ultraviolet A (UVA) radiation than those without the disorder. A newly synthesized molecule may provide protection when used as a sunscreen additive.
Friedrich’s Ataxia (FA) is an inherited, degenerative neuromuscular disorder that affects about one in 50,000 people in the United States. Individuals affected by the disorder inherit two mutated copies of the FXN gene from two parents who are both carriers of the disease.
Symptoms of the disorder include loss of coordination (ataxia) in the limbs; problems with vision, hearing and speech; scoliosis; and diabetes mellitus. Individuals with the disorder have an increased risk of dying in early adulthood, and there is currently no cure or effective treatment.
Friedrich’s Ataxia, along with conditions like Wolfram syndrome and Parkinson’s Disease, is characterized as a mitochondrial iron overload disorder. Iron is used for a whole host of processes within the mitochondria that are crucial for the production of energy (in the form of adenosine triphosphate [ATP]). When too much iron is combined with excess UVA rays, mitochondria can be depleted of ATP, and cells can die.
While UVA rays have the potential to damage cells in individuals without FA, the damage is worsened by extra mitochondrial iron because it encourages the formation of free radical species, namely reactive oxygen species (ROS). ROS can damage cellular biomolecules like proteins and DNA, which can lead to cell death or cancer.
In a news release, Charareh Pourzand of the University of Bath’s Department of Pharmacy and Pharmacology explained how this process negatively affects the body.
“There’s a vicious cycle — excess iron in the mitochondria means more reactive oxidizing species and more damage to cell constituents, resulting in cell functions being compromised. This situation leaves cells more sensitive to subsequent oxidative damage notably by environmental factors such as UVA of sunlight,” Pourzand said.
The new study obtained skin fibroblasts from patients with FA and exposed them to UVA radiation. They found that there was a higher amount of ROS present after the exposure. In response, the team created a molecule called an iron chelator which targets the mitochondria and scoops up excess iron to prevent it from reacting to make ROS.
In the lab, the team pre-treated the skin fibroblasts with the iron chelator and saw that it prevented cell death from UVA rays. Specifically, the molecule was shown to cause a two-fold reduction in mitochondrial membrane damage caused by reasonable quantities of the radiation.
In addition to elucidating the interaction between high levels of mitochondrial iron and UVA rays, the research team hopes to use their results to design sunscreens that could help people with disorders characterized by iron overload in the mitochondria.
While most sunscreens are effective against UVB rays, the only protection offered for UVA rays is usually just the reflective properties of the cream itself.
For individuals with FA or other disorders with the same mitochondrial signature, this may not be enough to prevent other serious complications. The team hopes that the iron chelator, or some version of it, could be used as an additive in sunscreens to enhance their protective properties for people affected by mitochondrial iron overload disorders.