Role of mitochondrial DNA in cancer and age-related diseases has been identified

Mitochondrial dysfunction has a systemic effect on the body, but the most pronounced damage is observed in organs with high levels of energy consumption, such as the brain and heart. The clinical manifestations of mtDNA mutations include migraines, muscle weakness, and progressive hearing and vision loss. For a long time, studying the specific mechanisms of these diseases was difficult due to the complexity of creating biological models: it could take several years to develop a single line of mice with a specific mutation.

Scientists at the Salk Institute have developed a new technology platform that significantly accelerates the study of mtDNA variations. The method relies on the use of a protein called mitochondrial DNA polymerase, which generates random mutations in mtDNA. The resulting genetic material is then transferred to stem cells, which are integrated into mouse embryos. This scalable approach has resulted in the creation of a library of 155 mutant cell lines, each with unique mitochondrial function characteristics.

The conducted tests confirmed the applicability of the platform for studying the early stages of life. The researchers found a direct correlation between the functional state of mitochondria and the success of embryonic development. This confirms the hypothesis of the existence of a basic energy threshold necessary for the normal formation of an organism. The scale of the created library is comparable to the diversity of known human pathogenic mutations, making it an important resource for translational medicine.

The prospects for using this development go beyond the treatment of rare hereditary syndromes. Mitochondrial dysfunction is a concomitant factor in the development of cancer and natural aging processes. The new platform allows for the modeling of mutations that occur not only as a result of heredity, but also under the influence of external factors or age-related changes. This accelerates the search for therapeutic targets and the development of drugs for the correction of cellular energy metabolism.

The introduction of such tools into research practice will allow for the systematization of knowledge about the impact of mtDNA variability on physiological adaptation and disease mechanisms. The researchers plan to adapt the platform for use with human models, which will bring us closer to developing personalized treatments for mitochondrial disorders and associated conditions.