Mitochondria interaction networks show altered topological patterns in Parkinson's disease.
Journal
NPJ systems biology and applications
ISSN: 2056-7189
Titre abrégé: NPJ Syst Biol Appl
Pays: England
ID NLM: 101677786
Informations de publication
Date de publication:
10 11 2020
10 11 2020
Historique:
received:
05
04
2020
accepted:
02
10
2020
entrez:
11
11
2020
pubmed:
12
11
2020
medline:
5
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33173039
doi: 10.1038/s41540-020-00156-4
pii: 10.1038/s41540-020-00156-4
pmc: PMC7655803
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
38Références
Am J Hum Genet. 2011 Jul 15;89(1):162-7
pubmed: 21763482
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7821-6
pubmed: 12060727
Nat Rev Neurosci. 2006 Mar;7(3):207-19
pubmed: 16495942
Hum Mol Genet. 2009 Oct 15;18(R2):R169-76
pubmed: 19808793
Nat Med. 2016 Jan;22(1):54-63
pubmed: 26618722
Sci Signal. 2011 Sep 06;4(190):tr5
pubmed: 21917719
PLoS One. 2013;8(3):e59252
pubmed: 23533608
PLoS One. 2011;6(11):e26159
pubmed: 22110584
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4323-8
pubmed: 18326631
Hum Mol Genet. 2020 May 28;29(8):1353-1364
pubmed: 32280985
Nature. 2009 Sep 10;461(7261):218-23
pubmed: 19741703
Nat Commun. 2019 Mar 4;10(1):1017
pubmed: 30833554
Nature. 1998 Jun 4;393(6684):440-2
pubmed: 9623998
Cells. 2020 Sep 10;9(9):
pubmed: 32927687
Science. 2003 Oct 31;302(5646):841
pubmed: 14593171
Hum Mol Genet. 2019 Jun 15;28(12):2001-2013
pubmed: 30753527
Antioxid Redox Signal. 2019 Dec 1;31(16):1213-1234
pubmed: 31303019
Biochim Biophys Acta. 2010 Jan;1802(1):2-10
pubmed: 19853658
Nat Rev Genet. 2011 Jan;12(1):56-68
pubmed: 21164525
J Neurochem. 2010 Jul;114(1):1-12
pubmed: 20403078
Nat Genet. 1998 Feb;18(2):106-8
pubmed: 9462735
Cell Stem Cell. 2011 Mar 4;8(3):267-80
pubmed: 21362567
Eur J Clin Invest. 2010 Nov;40(11):1048-60
pubmed: 20735469
Mov Disord. 2003 Jul;18(7):738-50
pubmed: 12815652
Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):311-6
pubmed: 16384916
Traffic. 2014 Feb;15(2):230-44
pubmed: 24152121
Nat Rev Neurosci. 2009 Mar;10(3):186-98
pubmed: 19190637
Nat Commun. 2014 Jun 06;5:4028
pubmed: 24905578
Nat Rev Neurosci. 2008 Jul;9(7):505-18
pubmed: 18568013
Phys Rev Lett. 2002 Nov 11;89(20):208701
pubmed: 12443515
Cell. 2011 Mar 18;144(6):986-98
pubmed: 21414488
J Neurochem. 1990 Mar;54(3):823-7
pubmed: 2154550
Science. 1999 Oct 15;286(5439):509-12
pubmed: 10521342
Bioinform Biol Insights. 2015 Apr 19;9:49-60
pubmed: 25983553
Cell Stem Cell. 2016 Dec 1;19(6):709-724
pubmed: 27618216
Curr Biol. 2014 Jul 21;24(14):1670-1676
pubmed: 24980502
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4447-52
pubmed: 15070738
J Bone Miner Res. 2013 Aug;28(8):1837-45
pubmed: 23494896
Cell Syst. 2017 Dec 27;5(6):564-577.e12
pubmed: 29128334
Brain Res. 2018 Aug 15;1693(Pt B):207-213
pubmed: 29360466
Mol Syst Biol. 2007;3:140
pubmed: 17940530
BMC Biol. 2013 Jun 24;11:71
pubmed: 23800141
Nature. 2000 Oct 5;407(6804):651-4
pubmed: 11034217
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5934-9
pubmed: 15079056
Stem Cell Res. 2020 May;45:101776
pubmed: 32387898
Nat Commun. 2019 Mar 4;10(1):1016
pubmed: 30833568
Cell Stem Cell. 2010 Nov 5;7(5):618-30
pubmed: 20888316
Front Neuroanat. 2015 Jul 08;9:91
pubmed: 26217195
Cell. 2007 Nov 30;131(5):861-72
pubmed: 18035408
Acta Neuropathol. 2010 Jun;119(6):689-702
pubmed: 20306269
Sci Rep. 2016 Sep 14;6:33117
pubmed: 27624977
Brief Funct Genomics. 2011 Sep;10(5):280-93
pubmed: 21764832
Cell Rep. 2017 Apr 18;19(3):487-496
pubmed: 28423313
Science. 2002 Oct 25;298(5594):824-7
pubmed: 12399590
Phys Rev Lett. 2001 Nov 5;87(19):198701
pubmed: 11690461
Nat Protoc. 2013 Feb;8(2):223-53
pubmed: 23306458