Proteases have an essential role in safeguarding cell survival by maintaining protein homeostasis, which is threatened by different internal and external insults. Some viruses like HIV or hepatitis C make use of proteases to multiply and spread inside our body. Therefore, protease inhibitors are commonly used as medical treatment against those illnesses. Mitochondria also have a specific set of proteases important for regulating every aspect of mitochondrial physiology, from energy production to response to stress or activation of cell-death programs.
Based on the results from a previous grant, Aleksandra Trifunovic and her team want to have a closer look on one mitochondrial protease called CLPXP. They were able to show that depletion of this specific protease in cells helped the mitochondria in stabilizing the respiratory chain and therefore maintaining the energy production. “Now we want to go further and test our hypothesis in animal models for mitochondrial diseases and see, if we can prolong the life and health span” Trifunovic says. “The last step would be to bring it on a translational level and help patients,” she adds. Currently no treatment is available for myriad of mitochondrial disorders and patients are often treated with cocktails of vitamins, cofactors and nutritional supplements that seem not to have a major impact on the disease progression. Therefore, another part of the project is screening for possible protease inhibitors, which could be used as drugs against mitochondrial diseases.