Long assumed to be destructive to tissues and cells, “free radicals” generated by the cell's mitochondria are actually beneficial to healing wounds, according to scientists from UC San Diego. They discovered that such reactive oxygen species are necessary for the proper healing of skin wounds in the laboratory roundworm C. elegans.
In a study (C. elegans Epidermal Wounding Induces a Mitochondrial ROS Burst that Promotes Wound Repair) published in Developmental Cell, the researchers found that free radicals generated in the mitochondria not only are necessary for skin wound healing, but that increased levels of reactive oxygen species (ROS) can actually make wounds heal faster.
“There are many ways you can generate ROS in the cell, but no one had looked in the mitochondria in detail,” said Andrew Chisholm, Ph.D., a professor of biology at UC San Diego, who carried out the research with Suhong Xu, Ph.D., a postdoctoral fellow in his laboratory. “Our discovery was surprising because we didn't realize that mitochondria were playing these roles in wound healing.”
“We find that the mitochondrial calcium uniporter MCU-1 is essential for rapid mitochondrial Ca2+ uptake and mtROS [mitochondrial ROS] production after wounding,” wrote the investigators. “mtROS can promote wound closure by local inhibition of Rho GTPase activity via a redox-sensitive motif. These findings delineate a pathway acting via mtROS that promotes cytoskeletal responses in wound healing.”
Free radicals have long been known to damage DNA, RNA, and proteins. Because such oxidative damage is thought to contribute to premature aging and cancer, many people take antioxidants to minimize the cellular damage from free radicals. However, the UC San Diego team found that while too much ROS in the cell may be bad for you, eliminating ROS altogether prevents wound healing, at least for roundworms. Their discovery has implications for the development of new pharmaceuticals to treat the elderly and people with diabetes who have chronic issues with wound healing.
“It appears you need some optimal level of ROS signaling,” explained Dr. Chisholm. “Too much is bad for you, but too little is also bad. We discovered in our experiments that when we knocked out the genes that produced ROS in the mitochondria and eliminated antioxidants, the roundworms had trouble closing up their wounds. We also found that a little more ROS helped the wounds close faster than normal.”
While the researchers have confirmed their results only for the roundworm, they believe it applies to higher animals and are planning to continue further investigations in rodents. “We suspect that these genetic pathways are conserved, so that they would apply to vertebrates and mammals as well,” predicted Dr. Chisholm.