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