Parkin and PINK1 mitigate STING-induced inflammation Parkin and PINK1, two proteins involved in mitochondrial quality control, play a critical role in preventing inflammation and neurodegeneration by removing damaged mitochondria through a process called mitophagy. This study shows that in the absence of Parkin or PINK1, mitochondrial dysfunction leads to the release of damage-associated molecular patterns (DAMPs), which activate innate immunity and promote inflammation. The study demonstrates that in Parkin and PINK1 deficient mice, exhaustive exercise (EE) and mitochondrial DNA mutations lead to increased inflammatory cytokines, which are significantly reduced when STING is also absent. STING is a key regulator of the type I interferon response to cytosolic DNA, and its loss rescues the inflammatory phenotype in these mice. The study also shows that Parkin and PINK1 deficiency leads to increased levels of inflammatory cytokines in humans, suggesting a similar role in human Parkinson's disease (PD). The findings indicate that mitophagy, mediated by Parkin and PINK1, is essential for preventing inflammation and neurodegeneration by clearing damaged mitochondria and reducing the release of mtDNA. The study highlights the importance of mitophagy in maintaining mitochondrial health and preventing inflammation in PD.Parkin and PINK1 mitigate STING-induced inflammation Parkin and PINK1, two proteins involved in mitochondrial quality control, play a critical role in preventing inflammation and neurodegeneration by removing damaged mitochondria through a process called mitophagy. This study shows that in the absence of Parkin or PINK1, mitochondrial dysfunction leads to the release of damage-associated molecular patterns (DAMPs), which activate innate immunity and promote inflammation. The study demonstrates that in Parkin and PINK1 deficient mice, exhaustive exercise (EE) and mitochondrial DNA mutations lead to increased inflammatory cytokines, which are significantly reduced when STING is also absent. STING is a key regulator of the type I interferon response to cytosolic DNA, and its loss rescues the inflammatory phenotype in these mice. The study also shows that Parkin and PINK1 deficiency leads to increased levels of inflammatory cytokines in humans, suggesting a similar role in human Parkinson's disease (PD). The findings indicate that mitophagy, mediated by Parkin and PINK1, is essential for preventing inflammation and neurodegeneration by clearing damaged mitochondria and reducing the release of mtDNA. The study highlights the importance of mitophagy in maintaining mitochondrial health and preventing inflammation in PD.