Mitochondria interaction networks show altered topological patterns in Parkinson's disease.

Autor: Zanin M; Instituto de Física Interdisciplinar y Sistemas Complejos IFISC (UIB-CSIC), E-07122, Palma de Mallorca, Spain.; Center for Biomedical Technology, Universidad Politécnica de Madrid, Campus of Montegancedo, E-28223, Pozuelo de Alarcón, Madrid, Spain., Santos BFR; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg.; Transversal Translational Medicine, Luxembourg Institute of Health (LIH), 1A-B, rue Thomas Edison, L-1445, Strassen, Luxembourg.; Disease Modeling and Screening Platform (DMSP), Luxembourg Institute of Systems Biomedicine, University of Luxembourg & Luxembourg Institute of Health, 6 avenue du Swing, L-4367, Belvaux, Luxembourg., Antony PMA; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg.; Disease Modeling and Screening Platform (DMSP), Luxembourg Institute of Systems Biomedicine, University of Luxembourg & Luxembourg Institute of Health, 6 avenue du Swing, L-4367, Belvaux, Luxembourg., Berenguer-Escuder C; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg., Larsen SB; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg., Hanss Z; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg., Barbuti PA; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg.; Transversal Translational Medicine, Luxembourg Institute of Health (LIH), 1A-B, rue Thomas Edison, L-1445, Strassen, Luxembourg., Baumuratov AS; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg., Grossmann D; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg., Capelle CM; Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg., Weber J; Centre Hospitalier de Luxembourg (CHL) 4, Rue Nicolas Ernest Barblé, L-1210, Luxembourg, Luxembourg., Balling R; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg., Ollert M; Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg.; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis (ORCA), University of Southern Denmark, 5000C, Odense, Denmark., Krüger R; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg.; Transversal Translational Medicine, Luxembourg Institute of Health (LIH), 1A-B, rue Thomas Edison, L-1445, Strassen, Luxembourg.; Centre Hospitalier de Luxembourg (CHL) 4, Rue Nicolas Ernest Barblé, L-1210, Luxembourg, Luxembourg., Diederich NJ; Centre Hospitalier de Luxembourg (CHL) 4, Rue Nicolas Ernest Barblé, L-1210, Luxembourg, Luxembourg., He FQ; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg. Feng.he@lih.lu.; Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg. Feng.he@lih.lu.; Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, D-45122, Essen, Germany. Feng.he@lih.lu.
Jazyk: angličtina
Zdroj: NPJ systems biology and applications [NPJ Syst Biol Appl] 2020 Nov 10; Vol. 6 (1), pp. 38. Date of Electronic Publication: 2020 Nov 10.
DOI: 10.1038/s41540-020-00156-4
Abstrakt: 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.
Databáze: MEDLINE
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