[en] Mitochondrial dysfunction is linked to pathogenesis of Parkinson's disease (PD). However, individual mitochondria-based analyses do not show a uniform feature in PD patients. Since mitochondria interact with each other, we hypothesize that PD-related features might exist in topological patterns of mitochondria interaction networks (MINs). Here we show that MINs formed nonclassical scale-free supernetworks in colonic ganglia both from healthy controls and PD patients; however, altered network topological patterns were observed in PD patients. These patterns were highly correlated with PD clinical scores and a machine-learning approach based on the MIN features alone accurately distinguished between patients and controls with an area-under-curve value of 0.989. The MINs of midbrain dopaminergic neurons (mDANs) derived from several genetic PD patients also displayed specific changes. CRISPR/CAS9-based genome correction of alpha-synuclein point mutations reversed the changes in MINs of mDANs. Our organelle-interaction network analysis opens another critical dimension for a deeper characterization of various complex diseases with mitochondrial dysregulation.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Zanin, Massimiliano; Instituto de Física Interdisciplinar y Sistemas Complejos IFISC > Center for Biomedical Technology, Universidad Politécnica de Madrid,
Santos, Bruno F. R.; Luxembourg Institute of Health - LIH > Transversal Translational Medicine
Antony, Paul ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Berenguer-Escuder, Clara
Larsen, Simone B.
Hanss, Zoé ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Barbuti, Peter ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Baumuratov, Aidos ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Grossmann, Dajana ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Capelle, Christophe M.; Luxembourg Institute of Health - LIH > Department of Infection and Immunity
Weber, Joseph; Centre Hospitalier de Luxembourg (CHL)
Balling, Rudolf ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Ollert, Markus; Luxembourg Institute of Health - LIH > Department of Infection and Immunity
Krüger, Rejko ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Diederich, Nico J.; Centre Hospitalier de Luxembourg (CHL)
He, Feng ; Luxembourg Institute of Health - LIH > Department of Infection and Immunity