Journal article
Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress
Journal of Neurochemistry, Vol.98(1), pp.156-169
2006
Abstract
Following our identification of PTEN-induced putative kinase 1 (PINK1) gene mutations in PARK6-linked Parkinson's disease (PD), we have recently reported that PINK1 protein localizes to Lewy bodies (LBs) in PD brains. We have used a cellular model system of LBs, namely induction of aggresomes, to determine how a mitochondrial protein, such as PINK1, can localize to aggregates. Using specific polyclonal antibodies, we firstly demonstrated that human PINK1 was cleaved and localized to mitochondria. We demonstrated that, on proteasome inhibition with MG-132, PINK1 and other mitochondrial proteins localized to aggresomes. Ultrastructural studies revealed that the mechanism was linked to the recruitment of intact mitochondria to the aggresome. Fractionation studies of lysates showed that PINK1 cleavage was enhanced by proteasomal stress in vitro and correlated with increased expression of the processed PINK1 protein in PD brain. These observations provide valuable insights into the mechanisms of LB formation in PD that should lead to a better understanding of PD pathogenesis. © 2006 International Society for Neurochemistry.
Details
- Title
- Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress
- Authors
- M M K Muqit (Author) - University College London, United KingdomP M Abou-Sleiman (Author) - University College London, United KingdomA T Saurin (Author) - Cancer Research UK, United KingdomK Harvey (Author) - University College London, United KingdomS Gandhi (Author) - University College London, United KingdomE Deas (Author) - University College London, United KingdomS Eaton (Author) - University College London, United KingdomM D Payne Smith (Author) - University College London, United KingdomK Venner (Author) - University College London, United KingdomA Matilla (Author) - University College London, United KingdomD G Healy (Author) - University College London, United KingdomW P Gilks (Author) - University College London, United KingdomA J Lees (Author) - University College London, United KingdomJ Holton (Author) - University College London, United KingdomT Revesz (Author)P J Parker (Author)Robert J Harvey (Author) - University College London, United KingdomN W Wood (Author) - University College London, United KingdomD S Latchman (Author) - University College London, United Kingdom
- Publication details
- Journal of Neurochemistry, Vol.98(1), pp.156-169
- Publisher
- Wiley-Blackwell Publishing Ltd.
- Date published
- 2006
- DOI
- 10.1111/j.1471-4159.2006.03845.x
- ISSN
- 0022-3042
- 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
- 99450517002621
- Output Type
- Journal article
Metrics
683 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites