Upregulated Parkin expression protects mitochondrial homeostasis in DJ-1 konckdown cells and cells overexpressing the DJ-1 L166P mutation

Chang, Chunyan; Wu, Guolu; Gao, Peiye; Yang, Ling; Liu, Wen; Zuo, Jiane

doi:10.1007/s11010-013-1884-3

Cited by 19 publications

(14 citation statements)

References 33 publications

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“…Since then, several hundred papers on DJ-1 function have been reported. In addition, genetic or functional interactions between DJ-1 and PINK1 or PARKIN have been reported (Ved et al 2005;Hao et al 2010;Kamp et al 2010;Thomas et al 2011;Joselin et al 2012;Chang et al 2014) as has mitochondrial localization of DJ-1 (Canet-Aviles et al 2004;Zhang et al 2005;Blackinton et al 2009;Ren et al 2011;Maita et al 2013;Cali et al 2015). It is generally well accepted that a decrease in DJ-1 activity or loss of the DJ-1 gene perturbs mitochondrial function Meulener et al 2005;Ved et al 2005;Hao et al 2010;Irrcher et al 2010;Krebiehl et al 2010;Larsen et al 2011;Shim et al 2011;Giaime et al 2012;Heo et al 2012;Ren et al 2012;Wang et al 2012;Minakawa et al 2013;Chang et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…It is generally well accepted that a decrease in DJ-1 activity or loss of the DJ-1 gene perturbs mitochondrial function Meulener et al 2005;Ved et al 2005;Hao et al 2010;Irrcher et al 2010;Krebiehl et al 2010;Larsen et al 2011;Shim et al 2011;Giaime et al 2012;Heo et al 2012;Ren et al 2012;Wang et al 2012;Minakawa et al 2013;Chang et al 2014). In addition, genetic or functional interactions between DJ-1 and PINK1 or PARKIN have been reported (Ved et al 2005;Hao et al 2010;Kamp et al 2010;Thomas et al 2011;Joselin et al 2012;Chang et al 2014) as has mitochondrial localization of DJ-1 (Canet-Aviles et al 2004;Zhang et al 2005;Blackinton et al 2009;Ren et al 2011;Maita et al 2013;Cali et al 2015). Because DJ-1 is highly reactive to hydrogen peroxide through oxidation of Cys106, and functions as an important regulator of redox metabolism (Kinumi et al 2004;Taira et al 2004), we can infer that DJ-1 maintains mitochondrial integrity by protecting it from oxidative stress such as that generated by reactive oxygen species.…”

Section: Introductionmentioning

confidence: 99%

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Unexpected mitochondrial matrix localization of Parkinson's disease‐related DJ‐1 mutants but not wild‐type DJ‐1

et al. 2016

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DJ-1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK7 locus. Consistent with the inferred correlation between Parkinson's disease and mitochondrial impairment, mitochondrial localization of DJ-1 and its implied role in mitochondrial quality control have been reported. However, the mechanism by which DJ-1 affects mitochondrial function remains poorly defined, and the mitochondrial localization of DJ-1 is still controversial. Here, we show the mitochondrial matrix localization of various pathogenic and artificial DJ-1 mutants by multiple independent experimental approaches including cellular fractionation, proteinase K protection assays, and specific immunocytochemistry. Localization of various DJ-1 mutants to the matrix is dependent on the membrane potential and translocase activity in both the outer and the inner membranes. Nevertheless, DJ-1 possesses neither an amino-terminal alpha-helix nor a predictable matrix-targeting signal, and a post-translocation processing-derived molecular weight change is not observed. In fact, wild-type DJ-1 does not show any evidence of mitochondrial localization at all. Such a mode of matrix localization of DJ-1 is difficult to explain by conventional mechanisms and implies a unique matrix import mechanism for DJ-1 mutants.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unexpected mitochondrial matrix localization of Parkinson's disease‐related DJ‐1 mutants but not wild‐type DJ‐1

et al. 2016

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“…The presence of viable mitochondria was identified by Mito-tracker green (Molecular Probes, Beyotime, Shanghai, China) staining as described by Chang et al (2014) with minor modifications. The stock solution of Mito-tracker green was prepared at a concentration of 1 mM in DMSO and stored at -20°C.…”

Section: Methodsmentioning

confidence: 99%

Docking Studies and Biological Evaluation of a Potential β-Secretase Inhibitor of 3-Hydroxyhericenone F from Hericium erinaceus

Chen

Yong²,

Yang³

et al. 2017

Front. Pharmacol.

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder, affecting approximately more than 5% of the population worldwide over the age 65, annually. The incidence of AD is expected to be higher in the next 10 years. AD patients experience poor prognosis and as a consequence new drugs and therapeutic strategies are required in order to improve the clinical responses and outcomes of AD. The purpose of the present study was to screen a certain number of potential compounds from herbal sources and investigate their corresponding mode of action. In the present study, the learning and memory effects of ethanol:water (8:2) extracts from Hericium erinaceus were evaluated on a dementia rat model. The model was established by intraperitoneal injection of 100 mg/kg/d D-galactose in rats. The results indicated that the extracts can significantly ameliorate the learning and memory abilities. Specific active ingredients were screened in vivo assays and the results were combined with molecular docking studies. Potential receptor–ligand interactions on the BACE1-inhibitor namely, 3-Hydroxyhericenone F (3HF) were investigated. The isolation of a limited amount of 3HF from the fruit body of H. erinaceus by chemical separation was conducted, and the mode of action of this compound was verified in NaN3-induced PC12 cells. The cell-based assays demonstrated that 3HF can significantly down-regulate the expression of BACE1 (p < 0.01), while additional AD intracellular markers namely, p-Tau and Aβ1-42 were further down-regulated (p < 0.05). The data further indicate that 3HF can ameliorate certain mitochondrial dysfunction conditions by the reversal of the decreasing level of mitochondrial respiratory chain complexes, the calcium ion levels ([Ca2+]), the inhibiton in the production of ROS, the increase in the mitochondrial membrane potential and ATP levels, and the regulation of the expression levels of the genes encoding for the p21, COX I, COX II, PARP1, and NF-κB proteins. The observations suggest the use of H. erinaceus in traditional medicine for the treatment of various neurological diseases and render 3HF as a promising naturally occurring chemical constituent for the treatment of AD via the inhibition of the β-secretase enzyme.

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“…Thus, it has been found that the physical interaction of these proteins protects cells against oxidative stress and promotes the degradation of unfolded proteins [12, 13]. However, other laboratories could not find such a physical interaction, and propose that DJ1 would either act on the same upstream pathway, or in parallel to Pink1/Parkin [14, 15] at protecting mitochondrial integrity [16, 17]. …”

Section: Introductionmentioning

confidence: 99%

DJ1 represses glycolysis and cell proliferation by transcriptionally up-regulating pink1

Requejo-Aguilar

López-Fabuel

Jiménez-Blasco

et al. 2015

Biochemical Journal

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DJ1 is a multifunctional protein whose mutations cause autosomal recessive early-onset Parkinson disease (PD). DJ1 loss of function disrupts mitochondrial function, but the signaling pathway whereby it interferes with energy metabolism is unknown. Here, we found that mouse embryonic fibroblasts obtained from DJ1-null (dj1-/-) mice showed higher glycolytic rate than those from wild type DJ1 (dj1+/+). This effect could be counteracted by the expression of the full-length cDNA encoding the wild type DJ1, but not its DJ1-L166P mutant form associated with PD. Loss of DJ1 increased hypoxiainducible factor-1α (Hif1α) protein abundance and cell proliferation. To understand the molecular mechanism responsible for these effects, we focused on PTEN-induced protein kinase-1 (Pink1), a PD-associated protein whose loss was recently reported to up-regulate glucose metabolism and to sustain cell proliferation (Requejo-Aguilar, Lopez-Fabuel, Fernandez, Martins, Almeida and Bolaños, 2014, Nature Communications 5, 4514). Noticeably, we found that the alterations in glycolysis, HIF1α and proliferation of DJ1-deficient cells were abrogated by the expression of Pink1. Moreover, we found that loss of DJ1 decreased pink1 mRNA and Pink1 protein levels, and that DJ1, by binding with Foxo3a transcription factor, directly interacted with pink1 promoter stimulating its transcriptional activity. These results indicate that DJ1 regulates cell metabolism and proliferation through Pink1.

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Upregulated Parkin expression protects mitochondrial homeostasis in DJ-1 konckdown cells and cells overexpressing the DJ-1 L166P mutation

Cited by 19 publications

References 33 publications

Unexpected mitochondrial matrix localization of Parkinson's disease‐related DJ‐1 mutants but not wild‐type DJ‐1

Unexpected mitochondrial matrix localization of Parkinson's disease‐related DJ‐1 mutants but not wild‐type DJ‐1

Docking Studies and Biological Evaluation of a Potential β-Secretase Inhibitor of 3-Hydroxyhericenone F from Hericium erinaceus

DJ1 represses glycolysis and cell proliferation by transcriptionally up-regulating pink1

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