Mutations in the gene that encodes a protein called adenine nucleotide translocator (ANT) cause a variety of conditions, such as heart disease and weakness of the eye muscles, but the underlying mechanism of how these mutations trigger disease has been unclear. Now, researchers at Penn Medicine discovered that ANT is critical for a quality control process called mitophagy—which helps to ensure the integrity of the mitochondria network by removing damaged mitochondria—and found that mutations that lead to a defective quality control system ultimately cause heart disease.
The findings, published in Nature, reveal the new and surprising function of ANT, a well-known protein that also contributes to the mitochondria’s ability to produce the chemical energy, or adenosine triphosphate (ATP), needed to fuel the body’s cells. Although it’s been known the mutations in the ANT gene cause diseases, including cardiomyopathy—a disease that makes it harder for one’s heart to pump blood to the rest of the body—research has shown that the mutations do not impact ANT’s ability to produce chemical energy, raising questions about how one would then get a disease.
“In revealing the link between ANT and mitophagy, and the impact mutations have on quality control, our findings change the way we think about the disease-causing mutations and enable us to focus our attention on the right pathway,” says the study’s corresponding author Zoltan Arany, a professor of cardiovascular medicine in the Perelman School of Medicine. “Now that we know these diseases are caused by defective quality control rather than a lack of ATP generation, we can start thinking about therapeutic approaches that improve the quality control.”
Read more at Penn Medicine News.