Key Takeaways
- A new chemical tool developed at UC Riverside helps preserve mitochondrial DNA and prevents disease-related degradation.
- This approach stops mtDNA loss before it can trigger inflammation and other health issues.
- The protected DNA retains functionality, offering potential for therapeutic applications.
Mitochondrial DNA Preservation Tool Developed
Environmental stressors can damage DNA, leading to serious health issues such as heart conditions, neurodegeneration, and chronic inflammation. Researchers at the University of California, Riverside (UCR) have developed a novel chemical probe that intervenes in the degradation process of mitochondrial DNA (mtDNA), potentially preventing these diseases.
The study, published in Angewandte Chemie International Edition, emphasizes the importance of mtDNA, which differs from nuclear DNA by holding unique genetic information crucial for cellular functions like energy production. While cells contain several copies of mtDNA, when damage occurs, these copies are frequently degraded instead of repaired. This degradation can interfere with tissue function and trigger inflammatory responses.
To combat this degradation, UCR researchers designed a chemical probe that specifically binds to damaged areas of mtDNA, blocking the harmful enzymatic processes that lead to loss. Instead of repairing the damage, the probe aims to reduce mtDNA loss, acting as a preventive measure.
Linlin Zhao, an associate professor of chemistry at UCR and the project leader, noted, “There are pathways in cells that attempt repair, but degradation occurs more frequently due to the redundancy of mtDNA. Our strategy is to stop the loss before it becomes a problem.”
The new chemical compound incorporates two vital elements: one for recognizing and attaching to damaged DNA, and another that delivers the molecule specifically to mitochondria, ensuring nuclear DNA remains unaffected. Anal Jana, a postdoctoral fellow in Zhao’s lab and the leading author, combined expertise in chemical synthesis with knowledge of DNA repair to design this innovative molecule.
In lab tests and studies involving living cells, the chemical probe successfully diminished mtDNA loss caused by damage that mimicked exposure to harmful environmental pollutants, like nitrosamines found in processed foods and tobacco smoke. Cells treated with the probe showed higher mtDNA levels, which is essential for maintaining energy production, particularly in sensitive tissues, such as the heart and brain.
Loss of mitochondrial DNA is increasingly associated with a variety of diseases, including mitochondrial depletion syndromes and chronic inflammatory conditions like diabetes, Alzheimer’s, and inflammatory bowel disease. When mtDNA fragments leak into the cytoplasm, they can trigger immune responses, leading to inflammation. Zhao explained, “If we can retain the DNA inside the mitochondria, we might be able to prevent those downstream signals that cause inflammation.”
Crucially, the researchers discovered that the chemically protected DNA remained functional, defying initial expectations that a bulky chemical attachment would inhibit its activity. Zhao commented, “We thought adding a bulky chemical might prevent the DNA from working properly. But to our surprise, it was still able to support transcription, the process cells use to turn DNA into RNA and then into proteins.” This discovery opens avenues for potential therapeutic applications, marking a significant shift in the approach to DNA defense under stress.
This groundbreaking research builds on over two years of investigation into the cellular mechanisms that regulate mtDNA processing. While further studies are needed to explore clinical implications, the new molecule represents a paradigm shift—it’s a chemical approach focused on prevention rather than just repair.
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