Mitochondrial DNA and Inflammation
Maintaining the integrity of mtDNA is vitally important to counter chronic inflammation and organ damage in many diseases of aging. Inflammation, an early immune response to microbial infection, is stimulated by chemical factors released by injured cells. This response prevents further spread of infection and promotes healing of damaged tissue following the clearance of pathogens. Inflammation is initiated by immune cells residing in tissues. Receptors on the surface, or within these immune cells, recognize molecular characteristics broadly shared by pathogens but distinguishable from host molecules. At the onset of an infection, burn, or other injuries, the immune cells are activated when one of the receptors recognizes a pathogenic signal. This results in the release of multiple inflammatory mediators that are responsible for the clinical signs of inflammation.
Proteins or nucleic acid sequences of bacterial RNA or DNA serve as immuno-stimulatory agents. Similarly, human cells release molecules which arise from cell damage or death to stimulate an inflammatory response.
Owing to the bacterial origin of mitochondria, mtDNA shares nucleic acid sequences present in modern day bacteria.
Mitochondria, under periods of stress or injury, release oxidized mtDNA fragments into the cytosol, the extracellular space, and the systemic circulation.
These ejected mtDNA fragments trigger activation of multiple pro-inflammatory pathways
that contribute to chronic inflammation. Maintaining the integrity of mtDNA, therefore, is a vitally important to counter inflammation in diseases of aging.