Mitochondrial DNA Damage Linked to Disease in New Research

Researchers at the University of California, Riverside, have unveiled a new type of mitochondrial DNA damage that could play a critical role in how the body responds to stress, according to a study published in the Proceedings of the National Academy of Sciences.

This study, led by Linlin Zhao, an associate professor of chemistry, highlights the significance of glutathionylated DNA, or GSH-DNA adducts, as a source of harm to mitochondrial DNA, or mtDNA. Mitochondria, the cell's energy-producing structures, contain their own genetic material, which is crucial for generating cellular energy and signaling both within and outside the cell.

While it has been known that mtDNA is susceptible to damage, the specifics have remained elusive until now. The research reveals that GSH-DNA adducts accumulate in mtDNA at levels up to eighty times higher than in nuclear DNA, which poses a significant risk for mutations and subsequent disease.

Yu Hsuan Chen, a doctoral student and the study's first author, compares damaged mtDNA to a manual with sticky notes that obscure important information. This type of damage can disrupt mitochondrial function, decreasing proteins necessary for energy production while increasing stress response proteins, indicating the cell's attempts to cope with the damage.

Zhao emphasizes that the discovery of these adducts could provide new pathways to explore how damaged mtDNA influences immune responses and inflammation, linking issues with mitochondria to diseases like neurodegeneration and diabetes.

As mtDNA can escape from mitochondria and trigger immune responses, understanding GSH-DNA adducts may lead to innovative treatments for various diseases associated with mitochondrial dysfunction. This collaborative research involved scientists from both UC Riverside and the University of Texas MD Anderson Cancer Center, funded by the National Institutes of Health and UC Riverside, underscoring the potential impact of this discovery on future genetic research and therapies.