Journal article
The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1
Nature Cell Biology, Vol.9(11), pp.1243-1252
2007
Abstract
In mice, targeted deletion of the serine protease HtrA2 (also known as Omi) causes mitochondrial dysfunction leading to a neurodegenerative disorder with parkinsonian features. In humans, point mutations in HtrA2 are a susceptibility factor for Parkinson's disease (PARK13 locus). Mutations in PINK1, a putative mitochondrial protein kinase, are associated with the PARK6 autosomal recessive locus for susceptibility to early-onset Parkinson's disease. Here we determine that HtrA2 interacts with PINK1 and that both are components of the same stress-sensing pathway. HtrA2 is phosphorylated on activation of the p38 pathway, occurring in a PINK1-dependent manner at a residue adjacent to a position found mutated in patients with Parkinson's disease. HtrA2 phosphorylation is decreased in brains of patients with Parkinson's disease carrying mutations in PINK1. We suggest that PINK1-dependent phosphorylation of HtrA2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress.
Details
- Title
- The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1
- Authors
- H Plun-Favreau (Author) - Cancer Research UK London Research Institute, United KingdomK Klupsch (Author) - Cancer Research UK London Research Institute, United KingdomN Moisoi (Author) - MRC Toxicology Unit, United KingdomS Gandhi (Author) - Institute of Neurology, United KingdomS Kjaer (Author) - Cancer Research UK London Research Institute, United KingdomD Frith (Author) - Cancer Research UK London Research Institute, United KingdomK Harvey (Author) - University College London, United KingdomE Deas (Author) - Institute of Neurology, United KingdomRobert J Harvey (Author) - University College London, United KingdomN McDonald (Author) - Cancer Research UK London Research Institute, United KingdomN W Wood (Author) - Institute of Neurology, United KingdomM L Martins (Author) - MRC Toxicology Unit, United KingdomJ Downward (Author) - Cancer Research UK London Research Institute, United Kingdom
- Publication details
- Nature Cell Biology, Vol.9(11), pp.1243-1252
- Publisher
- Nature Publishing Group
- Date published
- 2007
- DOI
- 10.1038/ncb1644
- ISSN
- 1465-7392
- 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
- 99450693602621
- Output Type
- Journal article
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