NIH Research Festival
Whereas mutations in PINK1 and Parkin, which function together to clear damaged mitochondria, lead to early onset Parkinson’s disease (PD) in humans, Parkin-/- and PINK1-/- mice display no substantial PD-related phenotypes. We hypothesized that the sedentary environment of laboratory mice may mask underlying phenotypes and, therefore, utilized exhaustive exercise to stress mitochondria in vivo. Consistent with reports that mitochondrial stress or damage can directly initiate inflammation, we found that following exercise, Parkin-/- and PINK1-/- mice, but not WT mice, displayed dramatically elevated levels of inflammatory cytokines, increased body temperature and muscle damage. Concurrent deletion of STING, an innate immune receptor which responds downstream of cGAS, a sensor of mtDNA, or treatment with anti-IFNAR1 antibodies rescued the inflammatory response. Our data link the loss PINK1 and Parkin to STING-mediated inflammation following mitochondrial stress and, importantly, suggest that mitophagy may mitigate PD by removing damaged mitochondria and their DNA.
Scientific Focus Area: Immunology
This page was last updated on Friday, March 26, 2021