Cheryl Walker, Ph.D., and her team at the Texas A&M Health Science Center (TAMHSC) Institute of Biosciences and Technology (IBT), made a discovery that could provide an answer to the 50-year mystery about a tiny intracellular organelle, peroxisomes. It was unclear how peroxisomes and the tuberous sclerosis complex (TSC2) work together for cell survival. However, in the recent study, the team discovered that TSC2 retains peroxisomes, which break down fat in human cells, at the right levels as a monitor. The study was published in the October issue of Nature Cell Biology.
“Without TSC2 to balance peroxisomes, healthy cells could proliferate in an uncontrolled way—just like cancer,” said Walker. “Knowing how TSC2 behaves to keep cells balanced could help us learn how to balance or counteract diseases like cancer and heart disease, as well as inflammation and maladies associated with aging. In short, it is a concept that could lead to cures.”
When peroxisomes work, the conversion of fat generates reactive oxygen species (ROS), which is similar to the harmful oxidants. If peroxisomes levels are too high and too much ROS is created, ROS could damage anything in the cell, including proteins, lipids and DNA. “In a way, the TSC2 is Mother Nature’s DIY antioxidant,” Walker said. “It recognizes when there is too much ROS so that our cells can protect themselves.”
In addition, peroxisomes have a unique feature to replicate themselves autonomously, and it could be another cause of generating too much ROS. Walker’s team found the role of TSC2 as a censor. Too much ROS prompts are signal from TSC2, and TSC2 notifies the cell to dispose the peroxisomes.
The new findings could provide new therapies for patients: “We have known for decades that some of the worst childhood diseases are caused by a lack of healthy peroxisomes,” said Dr. Walker. “The possibility that other diseases, such as cancers, may also be due to defective peroxisomes is totally unexpected, and this information enables the exciting possibility of new cancer therapies targeting the peroxisome.”