Groundbreaking chemical discovery protects mitochondrial DNA from damage, potentially preventing the onset of chronic diseases.
In a groundbreaking development, scientists at the University of California, Riverside have created a chemical probe designed to shield mitochondrial DNA (mtDNA) from toxic stress, potentially revolutionising the treatment of diseases linked to mtDNA damage.
Mitochondria, often referred to as the cell's powerhouses, are prone to damage by environmental stressors like pollution or toxic chemicals, leading to inflammation and tissue dysfunction. The mtDNA housed within these energy-producing structures is crucial for critical functions like energy production. Loss of mtDNA is increasingly associated with a wide range of diseases, from multi-organ mitochondrial depletion syndromes to chronic inflammatory conditions including diabetes, Alzheimer's, arthritis, and inflammatory bowel disease.
The newly developed chemical probe targets damage in mtDNA specifically, binding to damaged sites on the DNA and blocking the enzymatic degradation processes that usually destroy damaged mtDNA. This preservation of mtDNA lessens its loss during cellular stress and keeps the DNA intact and functional, thereby preventing the downstream harmful effects such as inflammation and tissue dysfunction which are linked to diseases like heart conditions, neurodegenerative disorders, and chronic inflammation.
The probe has a two-part design. One part recognises and attaches to damaged DNA regions, particularly abasic (AP) sites, while the other part targets the probe exclusively to mitochondria, avoiding interference with nuclear DNA. By chemically shielding the damaged mtDNA from degradation enzymes, the probe maintains higher mtDNA levels even after exposure to environmental toxins like nitrosamines found in cigarette smoke and processed food.
Importantly, although the DNA is chemically tagged by the probe, it remains capable of supporting vital cellular functions such as transcription and replication. This strategy enables cells to retain their mitochondrial genome, reducing the risk of energy production impairment and blocking inflammatory signaling caused when degraded mtDNA escapes mitochondria.
The findings of the study have been published in the German Chemical Society journal Angewandte Chemie International Edition. The potential use of the probe is to stop disease before it begins, especially diseases linked to damage in mitochondrial DNA such as Alzheimer's and heart failure. The development of the chemical probe is a testament to the ongoing advancements in medical research and the understanding of the cellular mechanisms involved in disease.
[1] [Link to the study] [3] [Link to another relevant study] [5] [Link to another relevant study]
The newly developed chemical probe targets damage in mitochondrial DNA (mtDNA) specifically, offering a potential innovation in health-and-wellness areas by reducing the risk of chronic diseases linked to mtDNA damage, such as Alzheimer's and heart failure. The chemical shielding of the mtDNA by the probe allows it to remain functional during cellular stress, thus preventing tissue dysfunction and inflammation associated with various medical-conditions like diabetes and arthritis. This probe could significantly contribute to the ongoing science and technology advancements in medical research, contributing to the understanding and treatment of a wide range of chronic diseases.
