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

Massimiliano Zanin, Bruno F.R. Santos, Paul M.A. Antony, Clara Berenguer-Escuder, Simone B. Larsen, Zoé Hanss, Peter A. Barbuti, Aidos S. Baumuratov, Dajana Grossmann, Christophe M. Capelle, Joseph Weber, Rudi Balling, Markus Ollert, Rejko Krüger, Nico J. Diederich, Feng Q. He*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Article number38
Journalnpj Systems Biology and Applications
Issue number1
Publication statusPublished - Dec 2020


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