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

被引：10

作者：

Zanin, Massimiliano ^{[1
,2
]}

Santos, Bruno F. R. ^{[3
,4
,5
,6
]}

Antony, Paul M. A. ^{[3
,5
,6
]}

Berenguer-Escuder, Clara ^{[3
]}

Larsen, Simone B. ^{[3
]}

Hanss, Zoe ^{[3
]}

Barbuti, Peter A. ^{[3
,4
]}

Baumuratov, Aidos S. ^{[3
]}

Grossmann, Dajana ^{[3
]}

Capelle, Christophe M. ^{[7
]}

Weber, Joseph ^{[8
]}

Balling, Rudi ^{[3
]}

Ollert, Markus ^{[7
,9
]}

Krueger, Rejko ^{[3
,4
,8
]}

Diederich, Nico J. ^{[8
]}

He, Feng Q. ^{[3
,7
,10
]}

机构：

[1] UIB CSIC, Inst Fis Interdisciplinar & Sistemas Complejos IF, E-07122 Palma De Mallorca, Spain

[2] Univ Politecn Madrid, Ctr Biomed Technol, Campus Montegancedo, E-28223 Madrid, Spain

[3] Univ Luxembourg, Luxembourg Ctr Syst Biomed LCSB, Campus Belval,6 Ave Swing, L-4367 Belvaux, Luxembourg

[4] Luxembourg Inst Hlth LIH, Transversal Translat Med, 1A-B Rue Thomas Edison, L-1445 Strassen, Luxembourg

[5] Univ Luxembourg, Dis Modeling & Screening Platform DMSP, Luxembourg Inst Syst Biomed, 6 Ave Swing, L-4367 Belvaux, Luxembourg

[6] Luxembourg Inst Hlth, 6 Ave Swing, L-4367 Belvaux, Luxembourg

[7] Luxembourg Inst Hlth LIH, Dept Infect & Immun, 29 Rue Henri Koch, L-4354 Esch Sur Alzette, Luxembourg

[8] Ctr Hosp Luxembourg CHL, 4 Rue Nicolas Ernest Barble, L-1210 Luxembourg, Luxembourg

[9] Univ Southern Denmark, Dept Dermatol & Allergy Ctr, Odense Res Ctr Anaphylaxis ORCA, DK-5000 Odense C, Denmark

[10] Univ Duisburg Essen, Inst Med Microbiol, Univ Hosp Essen, D-45122 Essen, Germany

来源：

NPJ SYSTEMS BIOLOGY AND APPLICATIONS | 2020年 / 6卷 / 01期

基金：

欧洲研究理事会;

关键词：

ALPHA-SYNUCLEIN; COMPLEX; DYNAMICS; DYSFUNCTION; MITOPHAGY; MUTATION; MOTIFS; CELLS;

D O I：

10.1038/s41540-020-00156-4

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 60 条

[1] Expanding insights of mitochondrial dysfunction in Parkinson's disease [J].