A new type of DNA damage in cells' powerhouses may fuel human diseases and inflammation

What is it about?

The cells' powerhouses, mitochondria, have their own genetic material, known as mitochondrial DNA (mtDNA). mtDNA is essential for producing the energy that powers our bodies and sending signals within and outside cells. While it has long been known that mtDNA is prone to damage, scientists didn't fully understand the biological processes. This research identifies a culprit: glutathionylated DNA (GSH-DNA) adducts. An adduct is a bulky chemical tag formed when a chemical, such as a carcinogen, attaches directly to DNA. If the damage isn’t repaired, it can lead to DNA mutations or an increased immune response, both of which increase the risk of disease. The researchers found a surprisingly high level of GSH-DNA adducts in mtDNA. The researchers linked the accumulation of the sticky lesions to significant changes in mitochondrial function. They observed a decrease in proteins required for energy production and a simultaneous increase in proteins involved in the stress response and mitochondrial repair, suggesting that the cell fights back against the damage. The researchers also determined how GSH-DNA adducts are repaired and how they affect DNA structure.

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Photo by MJH SHIKDER on Unsplash

Photo by MJH SHIKDER on Unsplash

Why is it important?

The documented abundance of GSH-DNA adducts in mitochondria underscores the importance of further investigating how these high levels of GSH-DNA adducts contribute to mitochondrial dysfunction. In addition, when mtDNA is damaged, it can escape from the mitochondria and trigger immune and inflammatory responses. The discovery of mitochondrial GSH-DNA adducts could open new avenues for understanding how they influence immune activity and inflammation.