Reference : Discordant Monozygotic Parkinson Disease Twins: Role of Mitochondrial Integrity

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/44688

Title :	Discordant Monozygotic Parkinson Disease Twins: Role of Mitochondrial Integrity
Language :	English
Author, co-author :	Dulovic-Mahlow, Marija* [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	König, Inke R.* [Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck > > > ; Universitätsklinikum Schleswig‐Holstein, Lübeck, Germany]
	Trinh, Joanne* [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Haissatou Diaw, Sokhna [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Urban, Peter P. [Department of Neurology, Asklepios Klinik Barmbek, Hamburg, Germany]
	Knappe, Evelyn [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Kuhnke, Neele [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Ingwersen, Lena-Christin [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Hinrichs, Frauke [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Weber, Joachim [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Kupnicka, Patrycja [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany > > > ; Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland]
	Balck, Alexander [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Delcambre, Sylvie [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Molecular and Functional Neurobiology >]
	Vollbrandt, Tillman [Cell Analysis Core Facility CAnaCore, Universität zu Lübeck, Lübeck, Germany]
	Grünewald, Anne [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Molecular and Functional Neurobiology >]
	Klein, Christine [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Seibler, Philip [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	Lohmann, Katja [Institute of Neurogenetics, University of Lübeck, Lübeck, Germany]
	* These authors have contributed equally to this work.
Publication date :	23-Oct-2020
Journal title :	Annals of Neurology
Publisher :	John Wiley & Sons
Peer reviewed :	Yes (verified by ORBilu)
Audience :	International
ISSN :	0364-5134
e-ISSN :	1531-8249
City :	Hoboken
Country :	NY
Abstract :	[en] Objective Even though genetic predisposition has proven to be an important element in Parkinson's disease (PD) etiology, monozygotic (MZ) twins with PD displayed a concordance rate of only about 20% despite their shared identical genetic background. Methods We recruited 5 pairs of MZ twins discordant for idiopathic PD and established skin fibroblast cultures to investigate mitochondrial phenotypes in these cellular models against the background of a presumably identical genome. To test for genetic differences, we performed whole genome sequencing, deep mitochondrial DNA (mtDNA) sequencing, and tested for mitochondrial deletions by multiplex real‐time polymerase chain reaction (PCR) in the fibroblast cultures. Further, the fibroblast cultures were tested for mitochondrial integrity by immunocytochemistry, immunoblotting, flow cytometry, and real‐time PCR to quantify gene expression. Results Genome sequencing did not identify any genetic difference. We found decreased mitochondrial functionality with reduced cellular adenosine triphosphate (ATP) levels, altered mitochondrial morphology, elevated protein levels of superoxide dismutase 2 (SOD2), and increased levels of peroxisome proliferator‐activated receptor‐gamma coactivator‐α (PPARGC1A) messenger RNA (mRNA) in skin fibroblast cultures from the affected compared to the unaffected twins. Further, there was a tendency for a higher number of somatic mtDNA variants among the affected twins. Interpretation We demonstrate disease‐related differences in mitochondrial integrity in the genetically identical twins. Of note, the clinical expression matches functional alterations of the mitochondria
Target :	Researchers
Permalink :	http://hdl.handle.net/10993/44688
DOI :	10.1002/ana.25942
FnR project :	FnR ; FNR9631103 > Anne Grünewald > Model IPD > Modelling idiopathic Parkinson’s disease-associated somatic variation in dopaminergic neurons > 01/01/2016 > 31/12/2020 > 2015

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