Newly Developed Chemical Probe Protects Mitochondrial DNA

Researchers at University of California Riverside have created a chemical probe that helps preserve mitochondrial DNA (mtDNA) following cellular stress, potentially interrupting processes linked to diseases such as heart conditions, neurodegeneration, and chronic inflammation.

Unlike nuclear DNA, which carries most genetic information, mitochondria possess their own smaller genome essential for energy production. Although mtDNA exists in multiple copies per cell, damage to these molecules usually results in degradation rather than repair. This loss can impair tissue function and trigger inflammation.

To counter this, the research team developed a molecule that binds specifically to damaged regions of mtDNA and prevents degradation by blocking enzymatic activity. “There are already pathways in cells that attempt repair,” explained Linlin Zhao, lead researcher of the study published in Angewandte Chemie International Edition. “But degradation happens more frequently than repair due to the redundancy of mtDNA molecules in mitochondria. Our strategy is to stop the loss before it becomes a problem.”

The new molecule includes two parts: one identifies and attaches to damaged DNA, and the other ensures it targets mitochondria, leaving nuclear DNA unaffected.

In lab and live cell experiments, the probe reduced mtDNA loss after induced damage simulating environmental toxic exposure. Treated cells maintained higher levels of mtDNA, especially crucial in tissues like the heart and brain.

Importantly, the researchers found that the protected DNA remained functional, despite being chemically tagged. “We thought adding a bulky chemical might prevent the DNA from working properly,” Zhao said. “But to our surprise, it was still able to support transcription, the process cells use to turn DNA into RNA, and then into proteins. That opens the door for therapeutic applications.”