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

doi:10.1038/s41540-020-00156-4

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

KI, OUH, Research Unit Dermatology and Allergology (Odense)

Instituto de Física Interdisciplinar y Sistemas Complejos IFISC (UIB-CSIC)
Technical University of Madrid
University of Luxembourg
Luxembourg Institute of Health
Luxembourg Hospital Centre
Essen University Hospital

Research output: Contribution to journal › Journal article › Research › peer-review

80 Downloads (Pure)

Abstract

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 language	English
Article number	38
Journal	npj Systems Biology and Applications
Volume	6
Number of pages	12
ISSN	2056-7189
DOIs	https://doi.org/10.1038/s41540-020-00156-4
Publication status	Published - Dec 2020

Funding

F.Q.H. was partially supported by Luxembourg National Research Fund (FNR) CORE programme grant (CORE/14/BM/8231540/GeDES), FNR AFR-RIKEN bilateral programme (TregBAR, F.Q.H. and M.O.), and PRIDE programme grants (PRIDE/ 11012546/NEXTIMMUNE and PRIDE/10907093/CRITICS). The work was also partially supported through intramural funding of LIH and LCSB through Ministry of Higher Education and Research (MESR) of Luxembourg. The cooperation was achieved through the European Cooperation in Science and Technology (eCOST) Action CA15120 OpenMultiMed. Fibroblasts were obtained from the Neuro-Biobank of the University of Tübingen, Germany. This biobank is supported by the local University, the Hertie Institute, and the DZNE. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 851255). M.Z. acknowledges the Spanish State Research Agency, through the Severo Ochoa and María de Maeztu Program for Centers and Units of Excellence in R&D (MDM-2017-0711).

Documents & Links

10.1038/s41540-020-00156-4Licence: CC BY

Open Access VersionFinal published version, 2.58 MBLicence: CC BY

SDU Link

Check access to the material in SDU Library's search engine

Cite this

Zanin, M., Santos, B. F. R., Antony, P. M. A., Berenguer-Escuder, C., Larsen, S. B., Hanss, Z., Barbuti, P. A., Baumuratov, A. S., Grossmann, D., Capelle, C. M., Weber, J., Balling, R., Ollert, M., Krüger, R., Diederich, N. J., & He, F. Q. (2020). Mitochondria interaction networks show altered topological patterns in Parkinson’s disease. npj Systems Biology and Applications, 6, Article 38. https://doi.org/10.1038/s41540-020-00156-4

@article{e46a1fcdbd7849529d9ada7b56ead4e4,

title = "Mitochondria interaction networks show altered topological patterns in Parkinson{\textquoteright}s disease",

abstract = "Mitochondrial dysfunction is linked to pathogenesis of Parkinson{\textquoteright}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.",

author = "Massimiliano Zanin and Santos, \{Bruno F.R.\} and Antony, \{Paul M.A.\} and Clara Berenguer-Escuder and Larsen, \{Simone B.\} and Zo{\'e} Hanss and Barbuti, \{Peter A.\} and Baumuratov, \{Aidos S.\} and Dajana Grossmann and Capelle, \{Christophe M.\} and Joseph Weber and Rudi Balling and Markus Ollert and Rejko Kr{\"u}ger and Diederich, \{Nico J.\} and He, \{Feng Q.\}",

year = "2020",

month = dec,

doi = "10.1038/s41540-020-00156-4",

language = "English",

volume = "6",

journal = "npj Systems Biology and Applications",

issn = "2056-7189",

publisher = "Nature Publishing Group",

}

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 2020, 'Mitochondria interaction networks show altered topological patterns in Parkinson’s disease', npj Systems Biology and Applications, vol. 6, 38. https://doi.org/10.1038/s41540-020-00156-4

TY - JOUR

T1 - Mitochondria interaction networks show altered topological patterns in Parkinson’s disease

AU - Zanin, Massimiliano

AU - Santos, Bruno F.R.

AU - Antony, Paul M.A.

AU - Berenguer-Escuder, Clara

AU - Larsen, Simone B.

AU - Hanss, Zoé

AU - Barbuti, Peter A.

AU - Baumuratov, Aidos S.

AU - Grossmann, Dajana

AU - Capelle, Christophe M.

AU - Weber, Joseph

AU - Balling, Rudi

AU - Ollert, Markus

AU - Krüger, Rejko

AU - Diederich, Nico J.

AU - He, Feng Q.

PY - 2020/12

Y1 - 2020/12

N2 - 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.

AB - 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.

UR - https://www.nature.com/articles/s41540-025-00552-8

U2 - 10.1038/s41540-020-00156-4

DO - 10.1038/s41540-020-00156-4

M3 - Journal article

C2 - 33173039

AN - SCOPUS:85095744360

SN - 2056-7189

VL - 6

JO - npj Systems Biology and Applications

JF - npj Systems Biology and Applications

M1 - 38

ER -

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

Abstract

Funding

Documents & Links

SDU Link

Other files and links

Fingerprint

Cite this