Reference : Human Dopaminergic Neurons Lacking PINK1 Exhibit Disrupted Dopamine Metabolism Relate...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/45258
Human Dopaminergic Neurons Lacking PINK1 Exhibit Disrupted Dopamine Metabolism Related to Vitamin B6 Co-Factors.
English
Bus, Christine [University of Tübingen > Department of Neurodegenerative Diseases, Centre of Neurology and Hertie Institute for Clinical Brain Research,]
Zizmare, Laimdota [> >]
Feldkaemper, Marita [> >]
Geisler, Sven [Univeristy of Tübingen > Department of Neurodegenerative Diseases, Centre of Neurology and Hertie Institute for Clinical Brain Research]
Zarani, Maria [Univerity of Tübingen > Department of Neurodegenerative Diseases, Centre of Neurology and Hertie Institute for Clinical Brain Research]
Schaedler, Anna [Univerity of Tübingen > Department of Neurodegenerative Diseases, Centre of Neurology and Hertie Institute for Clinical Brain Research]
Klose, Franziska [> >]
Admard, Jakob [> >]
Mageean, Craig J. [> >]
Arena, Giuseppe mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience]
Fallier-Becker, Petra [> >]
Ugun-Klusek, Aslihan [> >]
Maruszczak, Klaudia K. [> >]
Kapolou, Konstantina [Univerity of Tübingen]
Schmid, Benjamin [> >]
Rapaport, Doron [> >]
Ueffing, Marius [> >]
Casadei, Nicolas [> >]
Krüger, Rejko mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience]
Gasser, Thomas [University of Tübingen > Department of Neurodegenerative Diseases, Centre of Neurology and Hertie Institute for Clinical Brain Research]
Vogt Weisenhorn, Daniela M. [> >]
Kahle, Philipp J. [Department of Neurodegenerative Diseases, Centre of Neurology and Hertie Institute for Clinical Brain Research > University of Tübingen]
Trautwein, Christoph [> >]
Gloeckner, Christian J. [> >]
Fitzgerald, Julia C. [University of Tübingen > Department of Neurodegenerative Diseases, Centre of Neurology and Hertie Institute for Clinical Brain Research]
2020
iScience
23
12
101797
Yes (verified by ORBilu)
International
2589-0042
2589-0042
[en] Molecular Biology ; Molecular Neuroscience ; Omics ; Stem Cells Research
[en] PINK1 loss-of-function mutations cause early onset Parkinson disease. PINK1-Parkin mediated mitophagy has been well studied, but the relevance of the endogenous process in the brain is debated. Here, the absence of PINK1 in human dopaminergic neurons inhibits ionophore-induced mitophagy and reduces mitochondrial membrane potential. Compensatory, mitochondrial renewal maintains mitochondrial morphology and protects the respiratory chain. This is paralleled by metabolic changes, including inhibition of the TCA cycle enzyme mAconitase, accumulation of NAD(+), and metabolite depletion. Loss of PINK1 disrupts dopamine metabolism by critically affecting its synthesis and uptake. The mechanism involves steering of key amino acids toward energy production rather than neurotransmitter metabolism and involves cofactors related to the vitamin B6 salvage pathway identified using unbiased multi-omics approaches. We propose that reduction of mitochondrial membrane potential that cannot be controlled by PINK1 signaling initiates metabolic compensation that has neurometabolic consequences relevant to Parkinson disease.
http://hdl.handle.net/10993/45258
10.1016/j.isci.2020.101797
https://www.sciencedirect.com/science/article/pii/S2589004220309949#!
oA
© 2020 The Authors.
FnR ; FNR11676395 > Rejko Krüger > MiRisk-PD > Mitochondrial Risk factors in Parkinson's Disease > 01/03/2018 > 28/02/2021 > 2017

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