The Oxidation State of DJ-1 Regulates its Chaperone Activity Toward α-Synuclein

Zhou, Wenbo; Zhu, Min; Wilson, Mark A.; Petsko, Gregory A.; Fink, Anthony L.

doi:10.1016/j.jmb.2005.12.030

Cited by 329 publications

(309 citation statements)

References 61 publications

(72 reference statements)

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“…The crystal structures of YajL and DJ-1 are strikingly similar (Wilson et al, 2003(Wilson et al, , 2005, and their backbone structures are essentially identical (0.9 Å C a root-mean-square deviation), suggesting that they have similar functions. DJ-1 is involved in the cellular response to oxidative stress, and has been suggested to function as a weak protease (Lee et al, 2003), an oxidative stress-activated chaperone Shendelman et al, 2004;Zhou et al, 2006), an atypical peroxiredoxin-like peroxidase (Andres-Mateos et al, 2007;Canet-Avilés et al, 2004), a stabilizer of the antioxidant transcriptional regulator Nrf2 (Clements et al, 2006), an apoptosis inhibitor via interaction with Daxx (Junn et al, 2005), a transcriptional or translational regulator of gene expression (Cookson, 2005; van der Brug et al, 2008) and a regulator of uncoupling protein expression affecting the production of reactive oxygen species (Guzman et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Fermentation and alternative respiration compensate for NADH dehydrogenase deficiency in a prokaryotic model of DJ-1-associated Parkinsonism

Messaoudi

Gautier²,

Dairou

et al. 2015

Microbiology

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YajL is the closest prokaryotic homologue of Parkinson's disease-associated DJ-1, a protein of undefined function involved in the oxidative stress response. We reported recently that YajL and DJ-1 protect cells against oxidative stress-induced protein aggregation by acting as covalent chaperones for the thiol proteome, including the NuoG subunit of NADH dehydrogenase 1, and that NADH dehydrogenase 1 activity is negligible in the yajL mutant. We report here that this mutant compensates for low NADH dehydrogenase activity by utilizing NADH-independent alternative dehydrogenases, including pyruvate oxidase PoxB and D-amino acid dehydrogenase DadA, and mixed acid aerobic fermentations characterized by acetate, lactate, succinate and ethanol excretion. The yajL mutant has a low adenylate energy charge favouring glycolytic flux, and a high NADH/NAD ratio favouring fermentations over pyruvate dehydrogenase and the Krebs cycle. DNA array analysis showed upregulation of genes involved in glycolytic and pentose phosphate pathways and alternative respiratory pathways. Moreover, the yajL mutant preferentially catabolized pyruvate-forming amino acids over Krebs cycle-related amino acids, and thus the yajL mutant utilizes pyruvate-centred respiro-fermentative metabolism to compensate for the NADH dehydrogenase 1 defect and constitutes an interesting model for studying eukaryotic respiratory complex I deficiencies, especially those associated with Alzheimer's and Parkinson's diseases.

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Section: Introductionmentioning

confidence: 99%

Fermentation and alternative respiration compensate for NADH dehydrogenase deficiency in a prokaryotic model of DJ-1-associated Parkinsonism

Messaoudi

Gautier²,

Dairou

et al. 2015

Microbiology

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“…DJ-1 has three cysteines at amino acid numbers 46, 53 and 106 (C46, C53 and C106, respectively). Although oxidation of C106 is necessary for DJ-1 to exert its activity [11][12][13], further oxidation of C106 is thought to render DJ-1 inactive [14], and such oxidized DJ-1 has been observed in patients with the sporadic form of PD and Alzheimer disease [15,16].…”

Section: Introductionmentioning

confidence: 99%

DJ-1 binds to mitochondrial complex I and maintains its activity

Hayashi

Ishimori

Takahashi-Niki

et al. 2009

Biochemical and Biophysical Research Communications

176

122

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Parkinson's disease (PD) is caused by neuronal cell death, and oxidative stress and mitochondrial dysfunction are thought to be responsible for onset of PD. DJ-1, a causative gene product of a familial form of Parkinson's disease, PARK7, plays roles in transcriptional regulation and anti-oxidative stress. The possible mitochondrial function of DJ-1 has been proposed, but its exact function remains unclear. In this study, we found that DJ-1 directly bound to NDUFA4 and ND1, nuclear and mitochondrial DNA-encoding subunits of mitochondrial complex I, respectively, and was co-localized with complex I and that complex I activity was reduced in DJ-1-knockdown NIH3T3 and HEK293cells. These findings suggest that DJ-1 is an integral mitochondrial protein and that DJ-1 plays a role in maintenance of mitochondrial complex I activity.

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“…DJ-1 is conserved in bacteria, plants, animals, and humans (Lucas and Marin, 2007). It is well known that DJ-1 has multiple functions including anti-oxidant and chaperone functions associated with PD pathogenesis (Menzies et al, 2005;Xu et al, 2005;Zhou et al, 2006). However, DJ-1 deficiency or loss-of-function leads to oxidative stressinduced cell death in vitro and in vivo (Chen et al, 2005;Goldberg et al, 2005;Kim et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports have demonstrated that DJ-1 protein protects against neuronal cell death resulting from 6-OHDA-induced ROS. After exposure to dopaminergic neurotoxins including rotenone and 6-OHDA, intracellular ROS levels were inversely correlated with DJ-1 expression levels, suggesting that DJ-1 may mitigate 6-OHDA-induced oxidative stress and help protect cells against oxidative stress (Menzies et al, 2005;Xu et al, 2005;Zhou et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…It is highly conserved from human to Escherichia coli and is localized in the cytoplasm, nucleus, and mitochondria (Bonifati et al, 2003;Gupta et al, 2008;Lee et al, 2003;Wilson et al, 2004). This protein has multiple functions including antioxidant activity, chaperonelike properties, and transcriptional regulation (Menzies et al, 2005;Xu et al, 2005;Zhou et al, 2006). In addition, it is well known that the loss of the DJ-1 function by oxidative stress and mutation leads to human PD pathogenesis (Bonifati et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transduced Tat-DJ-1 Protein Protects against Oxidative Stress-Induced SH-SY5Y Cell Death and Parkinson Disease in a Mouse Model

Jeong

Kim

Woo

et al. 2012

Molecules and Cells

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Parkinson's disease (PD) is a well known neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compact (SN). Although the exact mechanism remains unclear, oxidative stress plays a critical role in the pathogenesis of PD. DJ-1 is a multifunctional protein, a potent antioxidant and chaperone, the loss of function of which is linked to the autosomal recessive early onset of PD. Therefore, we investigated the protective effects of DJ-1 protein against SH-SY5Y cells and in a PD mouse model using a cell permeable Tat-DJ-1 protein. Tat-DJ-1 protein rapidly transduced into the cells and showed a protective effect on 6-hydroxydopamine (6-OHDA)-induced neuronal cell death by reducing the reactive oxygen species (ROS). In addition, we found that Tat-DJ-1 protein protects against dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-induced PD mouse models. These results suggest that Tat-DJ-1 protein provides a potential therapeutic strategy for against ROS related human diseases including PD.

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The Oxidation State of DJ-1 Regulates its Chaperone Activity Toward α-Synuclein

Cited by 329 publications

References 61 publications

Fermentation and alternative respiration compensate for NADH dehydrogenase deficiency in a prokaryotic model of DJ-1-associated Parkinsonism

Fermentation and alternative respiration compensate for NADH dehydrogenase deficiency in a prokaryotic model of DJ-1-associated Parkinsonism

DJ-1 binds to mitochondrial complex I and maintains its activity

Transduced Tat-DJ-1 Protein Protects against Oxidative Stress-Induced SH-SY5Y Cell Death and Parkinson Disease in a Mouse Model

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