UC Riverside scientists have developed a chemical probe that protects mitochondrial DNA (mtDNA) from degradation caused by environmental stress a process linked to heart disease, neurodegeneration, and chronic inflammation.

The study, published in Angewandte Chemie International Edition, focuses on mtDNA, which plays a vital role in cellular energy production. Unlike nuclear DNA, mtDNA is more prone to degradation than repair, especially under stress. When mtDNA breaks down, it can impair tissue function and trigger harmful immune responses.

To counter this, the research team created a molecule that binds to damaged mtDNA and blocks the enzymes that normally degrade it. Rather than repairing the damage, this method helps preserve mtDNA levels before loss can cause harm.

The molecule is designed with two components: one that targets damaged DNA and another that directs it specifically to mitochondria, sparing the cell’s nucleus. In lab and cell based experiments, the probe significantly reduced mtDNA loss caused by toxic chemicals like nitrosamines, which are found in cigarette smoke, processed foods, and polluted water.

Importantly, the chemically tagged DNA remained functional, continuing to support normal cellular processes like transcription. This opens the door to therapeutic applications that could help prevent diseases associated with mtDNA loss, including Alzheimer’s, diabetes, arthritis, and mitochondrial depletion syndromes.

“This is a chemical approach to prevention, not just repair,” said lead researcher Linlin Zhao. “It’s a new way of thinking about how to defend the genome under stress.”

Source: https://news.ucr.edu/articles/2025/07/21/chemical-shield-stops-stressed-dna-triggering-disease