The PINK1/Parkin pathway of mitophagy exerts a protective effect during prion disease

Anne Ward; Forrest Jessop; Robert Faris; Jason Hollister; Daniel Shoup; Brent Race; Catharine M Bosio; Suzette A Priola

doi:10.1371/journal.pone.0298095

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The PINK1/Parkin pathway of mitophagy exerts a protective effect during prion disease

Journal article

Open access

Peer reviewed

The PINK1/Parkin pathway of mitophagy exerts a protective effect during prion disease

Anne Ward, Forrest Jessop, Robert Faris, Jason Hollister, Daniel Shoup, Brent Race, Catharine M Bosio and Suzette A Priola

PloS one, Vol.19(2), e0298095

02/23/2024

DOI: 10.1371/journal.pone.0298095

PMCID: PMC10889866

PMID: 38394123

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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 (PrPSc), 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.

Neurodegenerative Diseases

Animals

Mice

Mitophagy

Prion Diseases - genetics

Prions

Protein Kinases - genetics

Protein Kinases - metabolism

Reactive Oxygen Species - metabolism

Ubiquitin-Protein Ligases - genetics

Ubiquitin-Protein Ligases - metabolism

Details

Title: Subtitle: The PINK1/Parkin pathway of mitophagy exerts a protective effect during prion disease
Creators: Anne Ward - National Institute of Allergy and Infectious Diseases
Forrest Jessop - National Institute of Allergy and Infectious Diseases
Robert Faris - University of Iowa, Microbiology and Immunology
Jason Hollister - National Institute of Allergy and Infectious Diseases
Daniel Shoup - National Institute of Allergy and Infectious Diseases
Brent Race - National Institute of Allergy and Infectious Diseases
Catharine M Bosio - Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana
Suzette A Priola - National Institute of Allergy and Infectious Diseases
Resource Type: Journal article
Publication Details: PloS one, Vol.19(2), e0298095
DOI: 10.1371/journal.pone.0298095
PMID: 38394123
PMCID: PMC10889866
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: PLOS
Grant note: DOI: 10.13039/100006492, name: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, award: AI000752-27
Language: English
Date published: 02/23/2024
Academic Unit: Microbiology and Immunology
Record Identifier: 9984560748902771

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