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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
|---|---|
| Enthalten in: |
NPJ systems biology and applications - 6(2020), 1 vom: 10. Nov., Seite 38 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zanin, Massimiliano [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 04.10.2021 Date Revised 04.10.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41540-020-00156-4 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM317406876 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM317406876 | ||
| 003 | DE-627 | ||
| 005 | 20231225163210.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41540-020-00156-4 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1057.xml |
| 035 | |a (DE-627)NLM317406876 | ||
| 035 | |a (NLM)33173039 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zanin, Massimiliano |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mitochondria interaction networks show altered topological patterns in Parkinson's disease |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.10.2021 | ||
| 500 | |a Date Revised 04.10.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Santos, Bruno F R |e verfasserin |4 aut | |
| 700 | 1 | |a Antony, Paul M A |e verfasserin |4 aut | |
| 700 | 1 | |a Berenguer-Escuder, Clara |e verfasserin |4 aut | |
| 700 | 1 | |a Larsen, Simone B |e verfasserin |4 aut | |
| 700 | 1 | |a Hanss, Zoé |e verfasserin |4 aut | |
| 700 | 1 | |a Barbuti, Peter A |e verfasserin |4 aut | |
| 700 | 1 | |a Baumuratov, Aidos S |e verfasserin |4 aut | |
| 700 | 1 | |a Grossmann, Dajana |e verfasserin |4 aut | |
| 700 | 1 | |a Capelle, Christophe M |e verfasserin |4 aut | |
| 700 | 1 | |a Weber, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Balling, Rudi |e verfasserin |4 aut | |
| 700 | 1 | |a Ollert, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Krüger, Rejko |e verfasserin |4 aut | |
| 700 | 1 | |a Diederich, Nico J |e verfasserin |4 aut | |
| 700 | 1 | |a He, Feng Q |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t NPJ systems biology and applications |d 2015 |g 6(2020), 1 vom: 10. Nov., Seite 38 |w (DE-627)NLM258627204 |x 2056-7189 |7 nnns |
| 773 | 1 | 8 | |g volume:6 |g year:2020 |g number:1 |g day:10 |g month:11 |g pages:38 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41540-020-00156-4 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 6 |j 2020 |e 1 |b 10 |c 11 |h 38 | ||