Researchers in the University of Sheffield, England, have found out how mitochondria, the energy generators within cells, withstand attacks on their DNA from rogue molecules. Their findings could lead to new treatments for cancer and neurodegenerative diseases.
The five-year study, published last week in Science Advances, reveals how the enzyme TDP1, which is known to have a role in repairing damaged DNA in the cell’s nucleus, is also responsible for repairing damage to mitochondrial DNA (mtDNA).
Mitochondria are the powerhouses of cells. They generate the energy required for all cellular activity and have their own DNA. During the process of energy production and making proteins, a large amount of rogue reactive oxygen species are produced. They constantly attack the DNA in the mitochondria. These attacks break their DNA. However the new findings show mitochondria have their very own repair toolkits which are constantly active to maintain their own DNA integrity.
Lead author of the study, Professor Sherif El-Khamisy, a Wellcome Trust Investigator and Chair of Molecular Medicine at the University of Sheffield, said: “Each mitochondria repair toolkit has unique components – enzymes - which can cut, hammer and seal the breaks. The presence of these enzymes is important for energy production. Defects in repairing DNA breaks in the mitochondria affect vital organs that rely heavily on energy such as the brain. It also has implications on mitochondria replacement therapies recently approved in the UK and known as ‘three parent babies’.”
Having healthy mitochondria is also essential for tissue regeneration, making it particularly important for successful organ transplants.
Professor El-Khamisy believes the findings could pave the way for the development of new therapies for mitochondrial disease that boost their DNA repair capacity, or for cancer treatments which could use TDP1 inhibitors to prevent mtDNA repair selectively in cancer cells. “Cancer relies on cells dividing very quickly. That means they need a lot of energy, so will have really healthy mitochondria,” said Professor El-Khamisy. “If we can find a way to selectively damage the mitochondria in the cancer cells, by preventing or slowing its repair mechanism, this could be really promising.”
