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

November 10, 2020 By:
  • 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
  • Kruger R
  • Diederich NJ
  • He FQ.

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.

2020 Nov. NPJ Syst Biol Appl.6(1):38.
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