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


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.

Authors Zanin M, Santos BFR, Antony PMA, Berenguer-Escuder C, Larsen SB, Hanss Z, Barbuti PA, Baumuratov AS, Grossmann D, Capelle CM, Weber J, Balling R, Ollert M, Krüger R, Diederich NJ, He FQ
Journal NPJ systems biology and applications
Publication Date 2020 Nov 10;6(1):38
PubMed 33173039
PubMed Central PMC7655803
DOI 10.1038/s41540-020-00156-4

Research Projects

Cell Lines