UCLA

Mitochondrial dysfunction, a hallmark of aging and degenerative diseases, increases the production of mitochondrial Reactive Oxygen Spices and decreases the production of ATP. Damage mitochondria can result in the release of mitochondrial DNA (mtDNA) into the cytosol, where it acts as a damage-associated molecular pattern (DAMP) and triggers the activation of the immune response. Our study demonstrates that as flies age, there is an accumulation of cytosolic mtDNA. However, we found that improving mitochondrial function through the overexpression of Parkin during adulthood and DRP1 from midlife onwards effectively reduces the build-up of cytosolic mtDNA in both heads and thoraces of aged flies. Moreover, we observed a significant decrease in the expression of antimicrobial peptides (AMPs) and stress immune effectors. These findings highlight the potential of mitophagy-promoting interventions to mitigate cytosolic mtDNA accumulation and dampen the immune response activation in aging organisms. Therefore, promoting mitophagy may offer an effective approach to counteract the detrimental effects associated with cytosolic mtDNA accumulation and immune response activation in aging organisms.