Abstract
Mutations in the DJ-1 gene (also known as PARK7) cause inherited Parkinson's disease, which is characterized by neuronal death. Although DJ-1 is thought to be an antioxidant protein, the underlying mechanism by which loss of DJ-1 function contributes to cell death is unclear. Human DJ-1 and its Arabidopsis thaliana homologue, AtDJ-1a, are evolutionarily conserved proteins, indicating a universal function. To gain further knowledge of the molecular features associated with DJ-1 dysfunction, we have characterized AtDJ-1a. We show that AtDJ-1a levels are responsive to stress treatment and that AtDJ-1a loss of function results in accelerated cell death in aging plants. By contrast, transgenic plants with elevated AtDJ-1a levels have increased protection against environmental stress conditions, such as strong light, H(2)O(2), methyl viologen and copper sulfate. We further identify superoxide dismutase 1 (SOD1) and glutathione peroxidase 2 (GPX2) as interaction partners of both AtDJ-1a and human DJ-1, and show that this interaction results in AtDJ-1a- and DJ-1-mediated cytosolic SOD1 activation in a copper-dependent fashion. Our data have highlighted a conserved molecular mechanism for DJ-1 and revealed a new protein player in the oxidative stress response of plants.
Highlights
Parkinson’s disease (PD) is a multifaceted chronic neurodegenerative disease characterized by early and extensive loss of dopaminergic neurons in the pars compacta of the substantia nigra
Reports suggest that DJ-1/PARK7 translocates to mitochondria in response to C106 oxidation (Canet-Aviles et al, 2004); we observed only isolated cases of mitochondriatargeted AtDJ-1a in Arabidopsis
Because superoxide dismutase (SOD) catalyses the dismutation of damaging superoxide radicals to oxygen and H2O2, which in turn is converted into H2O by glutathione peroxidase 2 (GPX2) (Raha and Robinson, 2000), we addressed whether AtDJ-1a has a functional interaction with these enzymes
Summary
Parkinson’s disease (PD) is a multifaceted chronic neurodegenerative disease characterized by early and extensive loss of dopaminergic neurons in the pars compacta of the substantia nigra. Genetic lesions have been associated with early- and late-onset PD (Bonifati et al, 2003; Kitada et al, 1998; Paisan-Ruiz et al, 2004; Polymeropoulos et al, 1997; Valente et al, 2004; Zimprich et al, 2004). Mutations in DJ-1/PARK7 cause early-onset Parkinsonism with abnormalities in the dopaminergic system resembling those of sporadic PD (Bonifati et al, 2003; van Duijn et al, 2001). Evidence has demonstrated that DJ-1/PARK7 is responsive to oxidative stress, indicating a protection role against harsh conditions (CanetAviles et al, 2004; Gu et al, 2009; Kim et al, 2005; Martinat et al, 2004; Meulener et al, 2006); its precise mode of action remains unknown
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