AI Summary
is through inflammation, which is a normal immune response. However, when inflammation becomes chronic, it can contribute to various diseases, including lupus and rheumatoid arthritis. In this study, scientists have discovered a mechanism that leads to inflammation when mitochondrial DNA (mtDNA) escapes from the mitochondria and enters the cell's cytoplasm. This misplaced mtDNA is recognized as foreign DNA and activates a pathway that promotes inflammation. The researchers used imaging and cell biology techniques to track the process of mtDNA moving out of the mitochondria. By understanding this pathway, they hope to develop therapeutics that can disrupt the inflammatory response and reduce inflammation in aging and diseases. Overall, this research provides new insights into the role of mtDNA in promoting inflammation and offers potential targets for therapeutic interventions to mitigate inflammation in various diseases.
Cells in the human body contain power-generating mitochondria, each with their own mtDNA-;a unique set of genetic instructions entirely separate from the cell’s nuclear DNA that mitochondria use to create life-giving energy. When mtDNA remains where it belongs (inside of mitochondria), it sustains both mitochondrial and cellular health-;but when it goes where it doesn’t belong, it can initiate an immune response that promotes inflammation.
Now, Salk scientists and collaborators at UC San Diego have discovered a novel mechanism used to remove improperly functioning mtDNA from inside to outside the mitochondria. When this happens, the mtDNA gets flagged as foreign DNA and activates a cellular pathway normally used to promote inflammation to rid the cell of pathogens, like viruses.
The findings, published in Nature Cell Biology on February 8, 2024, offer many new targets for therapeutics to disrupt the inflammatory pathway and therefore mitigate inflammation during aging and diseases, like lupus or rheumatoid arthritis.
We knew that mtDNA was escaping mitochondria, but how was still unclear. Using imaging and cell biology approaches, we’re able to trace the steps of the pathway for moving mtDNA out of the mitochondria, which we can now try to target with therapeutic interventions to hopefully prevent the resulting inflammation.”
Professor Gerald Shadel, senior and co-corresponding author, director of the San Diego-Nathan Shock Center of Excellence in the Basic Biology of Aging and holder of the Audrey Geisel Chair in Biomedical Science at Salk
One of the ways our cells respond to damage and infection