Reference : Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/26526
Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism
English
Meiser, Johannes mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Delcambre, Sylvie mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Wegner, André mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Jäger, Christian mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Ghelfi, Jenny mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Fouquier d'Hérouël, Aymeric mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Dong, Xiangyi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Weindl, Daniel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Stautner, Constantin [Helmholtz Zentrum München - HZM > Institute of Developmental Genetics]
Nonnenmacher, Yannic mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Michelucci, Alessandro mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Popp, Oliver [Max-Delbrueck Center for Molecular Medicine - MDC > Mass Spectrometry Core Facility]
Giesert, Florian [Helmholtz Zentrum München - HZM > Institute of Developmental Genetics]
Schildknecht, Stefan [University of Konstanz - UK > Doerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine]
Kraemer, Lisa mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Schneider, Jochen G. mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > > > > > ; Saarland University Medical Center - UKS > Department of Internal Medicine II]
Woitalla, Dirk [Ruhr-University - RUB > St. Josef Hospital > Neurology]
Wurst, Wolfgang [Helmholtz Zentrum München - HZM > Institute of Developmental Genetics > > ; Deutsches Zentrum fur Neurodegenerative Erkrankungen e. V. - DZNE > > > ; Ludwig-Maximilians-Universität München - LMU > Adolf-Butenandt-Institut > Munich Cluster for Systems Neurology (SyNergy)]
Skupin, Alexander mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > > ; University of California San Diego - UCSD > National Center for Microscopy and Imaging Research]
Vogt Weisenhorn, Daniela M. [Helmholtz Zentrum München - HZM > Institute of Developmental Genetics]
Krüger, Rejko mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Leist, Marcel [University of Konstanz - UK > Doerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine]
Hiller, Karsten mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
2016
Neurobiology of disease
89
112-125
Yes (verified by ORBilu)
International
0969-9961
1095-953X
[en] Folate mediated one-carbon metabolism ; GC/MS ; Glutamine ; Glutathione ; Mitochondrial metabolism ; Oxidative stress ; Parkinson's disease ; ROS ; Serine ; Stable isotope-assisted metabolomics
[en] The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have been described as a causative factor in Parkinson's disease (PD). DJ-1 has an important function in cellular antioxidant responses, but its role in central metabolism of neurons is still elusive. We applied stable isotope assisted metabolic profiling to investigate the effect of a functional loss of DJ-1 and show that DJ-1 deficient neuronal cells exhibit decreased glutamine influx and reduced serine biosynthesis. By providing precursors for GSH synthesis, these two metabolic pathways are important contributors to cellular antioxidant response. Down-regulation of these pathways, as a result of loss of DJ-1 leads to an impaired antioxidant response. Furthermore, DJ-1 deficient mouse microglia showed a weak but constitutive pro-inflammatory activation. The combined effects of altered central metabolism and constitutive activation of glia cells raise the susceptibility of dopaminergic neurons towards degeneration in patients harboring mutated DJ-1. Our work reveals metabolic alterations leading to increased cellular instability and identifies potential new intervention points that can further be studied in the light of novel translational medicine approaches.
Researchers ; Professionals ; Students
http://hdl.handle.net/10993/26526
10.1016/j.nbd.2016.01.019
Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FnR ; FNR3951509 > Karsten Hiller > Metabolomics > Metabolomics Junior Research Group > 15/09/2010 > 14/09/2015 > 2010

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mmc1.mp4LUHMES shDJ-1 - mitochondrial motion analysis using TMRM staining and time lapse microscopy6.96 MBView/Open
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mmc2.mp4LUHMES shCtrl - mitochondrial motion analysis using TMRM staining and time lapse microscopy4.39 MBView/Open
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mmc3.xlsInformation on single ion mode (SIM) GC/MS analysis for determination of MIDs9 kBView/Open
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mmc4.xlsPrimer sequences used for qPCR8.5 kBView/Open
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mmc5.pdfSupplementary Figures S1 - S61.1 MBView/Open

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