1. The PINK1/Parkin pathway of mitophagy exerts a protective effect during prion disease.
- Author
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Ward, Anne, Jessop, Forrest, Faris, Robert, Hollister, Jason, Shoup, Daniel, Race, Brent, Bosio, Catharine M., and Priola, Suzette A.
- Subjects
PRION diseases ,PARKINSON'S disease ,REACTIVE oxygen species ,BRAIN diseases ,PRIONS - Abstract
The PINK1/Parkin pathway of mitophagy has been implicated in the pathogenesis of Parkinson's disease. In prion diseases, a transmissible neurodegenerative disease caused by the misfolded and infectious prion protein (PrP
Sc ), expression of both PINK1 and Parkin are elevated, suggesting that PINK1/Parkin mediated mitophagy may also play a role in prion pathogenesis. Using mice in which expression of either PINK1 (PINK1KO ) or Parkin (ParkinKO ) has been ablated, we analyzed the potential role of PINK1 and Parkin in prion pathogenesis. Prion infected PINK1KO and ParkinKO mice succumbed to disease more rapidly (153 and 150 days, respectively) than wild-type control C57Bl/6 mice (161 days). Faster incubation times in PINK1KO and ParkinKO mice did not correlate with altered prion pathology in the brain, altered expression of proteins associated with mitochondrial dynamics, or prion-related changes in mitochondrial respiration. However, the expression level of mitochondrial respiration Complex I, a major site for the formation of reactive oxygen species (ROS), was higher in prion infected PINK1KO and ParkinKO mice when compared to prion infected control mice. Our results demonstrate a protective role for PINK1/Parkin mitophagy during prion disease, likely by helping to minimize ROS formation via Complex I, leading to slower prion disease progression. [ABSTRACT FROM AUTHOR]- Published
- 2024
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