[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
Disciplines :
Biochemistry, biophysics & molecular biology
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
