Journal article
Distinct Mechanisms of Pathogenic DJ-1 Mutations in Mitochondrial Quality Control
Frontiers in Molecular Neuroscience, Vol.11, 68
2018
Abstract
The deglycase and chaperone protein DJ-1 is pivotal for cellular oxidative stress responses and mitochondrial quality control. Mutations in PARK7, encoding DJ-1, are associated with early-onset familial Parkinson's disease and lead to pathological oxidative stress and/or disrupted protein degradation by the proteasome. The aim of this study was to gain insights into the pathogenic mechanisms of selected DJ-1 missense mutations, by characterizing protein-protein interactions, core parameters of mitochondrial function, quality control regulation via autophagy, and cellular death following dopamine accumulation. We report that the DJ-1M26I mutant influences DJ-1 interactions with SUMO-1, in turn enhancing removal of mitochondria and conferring increased cellular susceptibility to dopamine toxicity. By contrast, the DJ-1D149A mutant does not influence mitophagy, but instead impairs Ca2+ dynamics and free radical homeostasis by disrupting DJ-1 interactions with a mitochondrial accessory protein known as DJ-1-binding protein (DJBP/EFCAB6). Thus, individual DJ-1 mutations have different effects on mitochondrial function and quality control, implying mutation-specific pathomechanisms converging on impaired mitochondrial homeostasis.
Details
- Title
- Distinct Mechanisms of Pathogenic DJ-1 Mutations in Mitochondrial Quality Control
- Authors
- Daniela Strobbe (Author) - University of Rome, ItalyAlexis A Robinson (Author) - University College London, United KingdomKirsten Harvey (Author) - University of London, United KingdomLara Rossi (Author) - University of Rome, ItalyCaterina Ferranina (Author) - University of Rome, ItalyValerio de Biase (Author) - University of London, United KingdomCarlo Rodolfo (Author) - University of Rome, ItalyRobert J Harvey (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and EngineeringMichelangelo Campanella (Author) - Regina Elena National Cancer Institute, Italy
- Publication details
- Frontiers in Molecular Neuroscience, Vol.11, 68; 15
- Publisher
- Frontiers Research Foundation
- Date published
- 2018
- DOI
- 10.3389/fnmol.2018.00068
- ISSN
- 1662-5099
- Copyright note
- Copyright © 2018 Strobbe, Robinson, Harvey, Rossi, Ferraina, de Biase, Rodolfo, Harvey and Campanella. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99451406102621
- Output Type
- Journal article
Metrics
12 File views/ downloads
700 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Web Of Science research areas
- Neurosciences
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites