Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling.
Mitofusin 2
angiogenesis
brain injury
brain repair
calcium imaging
contact sites
metabolism
mitochondrial dynamics
perivascular endfeet
proteomics
synthetic linker
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
07 04 2020
07 04 2020
Historique:
received:
18
06
2019
revised:
03
01
2020
accepted:
03
03
2020
pubmed:
30
3
2020
medline:
4
9
2021
entrez:
30
3
2020
Statut:
ppublish
Résumé
Astrocytes have emerged for playing important roles in brain tissue repair; however, the underlying mechanisms remain poorly understood. We show that acute injury and blood-brain barrier disruption trigger the formation of a prominent mitochondrial-enriched compartment in astrocytic endfeet, which enables vascular remodeling. Integrated imaging approaches revealed that this mitochondrial clustering is part of an adaptive response regulated by fusion dynamics. Astrocyte-specific conditional deletion of Mitofusin 2 (Mfn2) suppressed perivascular mitochondrial clustering and disrupted mitochondria-endoplasmic reticulum (ER) contact sites. Functionally, two-photon imaging experiments showed that these structural changes were mirrored by impaired mitochondrial Ca
Identifiants
pubmed: 32220306
pii: S1550-4131(20)30120-0
doi: 10.1016/j.cmet.2020.03.005
pmc: PMC7139200
pii:
doi:
Substances chimiques
GTP Phosphohydrolases
EC 3.6.1.-
Mfn2 protein, mouse
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
791-808.e8Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing financial interests.
Références
Biochem Biophys Res Commun. 2018 May 27;500(1):17-25
pubmed: 28676398
J Cereb Blood Flow Metab. 2017 Jul;37(7):2320-2339
pubmed: 28378621
Proc Natl Acad Sci U S A. 2016 May 3;113(18):E2536-45
pubmed: 27091993
J Cell Biol. 2014 Mar 17;204(6):919-29
pubmed: 24616225
Nat Commun. 2019 Mar 20;10(1):1287
pubmed: 30894536
Nat Commun. 2018 Jan 4;9(1):70
pubmed: 29302033
J Neurosci. 2014 Apr 23;34(17):5965-70
pubmed: 24760855
Folia Neuropathol. 2015;53(3):173-92
pubmed: 26443309
J Neurosci. 2012 Feb 29;32(9):3131-41
pubmed: 22378886
Nature. 2008 Dec 4;456(7222):605-10
pubmed: 19052620
Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):303-312
pubmed: 30541894
Nat Neurosci. 2015 Jul;18(7):942-52
pubmed: 26108722
Glia. 2018 Jun;66(6):1213-1234
pubmed: 29098734
Science. 2017 May 19;356(6339):
pubmed: 28522470
Neuron. 2017 Feb 8;93(3):587-605.e7
pubmed: 28132831
EMBO J. 2017 Aug 1;36(15):2187-2203
pubmed: 28637793
Trends Cell Biol. 2009 Feb;19(2):81-8
pubmed: 19144519
Nat Neurosci. 2010 Jan;13(1):133-40
pubmed: 20023653
Nat Neurosci. 2011 Aug 30;14(11):1481-8
pubmed: 21878933
Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1218-23
pubmed: 9448312
Nature. 2017 Jan 26;541(7638):481-487
pubmed: 28099414
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2174-81
pubmed: 25870285
Neuron. 2014 Apr 16;82(2):413-29
pubmed: 24742463
J Cell Biol. 2003 Jan 20;160(2):189-200
pubmed: 12527753
Glia. 2006 Jul;54(1):21-34
pubmed: 16652340
Nat Cell Biol. 2011 May;13(5):589-98
pubmed: 21478857
Nat Cell Biol. 2004 Sep;6(9):872-83
pubmed: 15322553
Front Neurol. 2014 Jun 04;5:82
pubmed: 24926283
Nature. 2011 Jun 19;476(7360):336-40
pubmed: 21685888
Cell. 2007 Aug 10;130(3):548-62
pubmed: 17693261
Sci Transl Med. 2012 Aug 15;4(147):147ra111
pubmed: 22896675
Mol Cell. 2013 Feb 7;49(3):487-98
pubmed: 23317502
J Clin Invest. 2017 Aug 1;127(8):3136-3151
pubmed: 28737509
J Neurosci. 2012 May 2;32(18):6391-410
pubmed: 22553043
J Bioenerg Biomembr. 2015 Apr;47(1-2):13-31
pubmed: 25248415
Hum Mol Genet. 2012 Nov 15;21(22):4827-35
pubmed: 22914740
Nat Rev Mol Cell Biol. 2018 Nov;19(11):713-730
pubmed: 30143745
Eur J Cell Biol. 2012 Jan;91(1):10-6
pubmed: 21397981
Cell Metab. 2018 May 01;27(5):1007-1025.e5
pubmed: 29657030
Trends Cell Biol. 2018 Jul;28(7):523-540
pubmed: 29588129
Neuron. 2017 Sep 27;96(1):17-42
pubmed: 28957666
Transgenic Res. 2008 Oct;17(5):919-28
pubmed: 18483774
Immunity. 2017 Jun 20;46(6):957-967
pubmed: 28636962
Mol Cell. 2016 Jul 21;63(2):240-248
pubmed: 27397688
Nat Rev Neurosci. 2015 May;16(5):249-63
pubmed: 25891508
Cell Discov. 2017 Mar 28;3:17005
pubmed: 28377822
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15927-32
pubmed: 15509649
Neuron. 2016 Dec 21;92(6):1308-1323
pubmed: 28009276
Cell Metab. 2019 Jun 4;29(6):1258-1273.e11
pubmed: 30930170
J Gen Virol. 2003 Jun;84(Pt 6):1613-1621
pubmed: 12771432
Glia. 2010 Jul;58(9):1094-103
pubmed: 20468051
Nat Rev Mol Cell Biol. 2012 Sep;13(9):566-78
pubmed: 22850819
Cell Metab. 2011 Dec 7;14(6):724-38
pubmed: 22152301
Cell Metab. 2013 Dec 3;18(6):844-59
pubmed: 24315370
J Gen Physiol. 2013 May;141(5):633-47
pubmed: 23589582
Cell. 2013 Sep 26;155(1):172-87
pubmed: 24074867
Nat Cell Biol. 2009 Aug;11(8):958-66
pubmed: 19578372
Nat Cell Biol. 2017 Aug;19(8):876-882
pubmed: 28714972
Trends Cell Biol. 2016 Apr;26(4):300-312
pubmed: 26896246
J Neurosci. 2009 Sep 16;29(37):11511-22
pubmed: 19759299
Nat Rev Neurosci. 2014 May;15(5):327-35
pubmed: 24739787
Nat Neurosci. 2019 Oct;22(10):1731-1742
pubmed: 31501572
Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):11249-11254
pubmed: 27647893
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13063-13068
pubmed: 27799543
J Cell Biol. 2017 Apr 3;216(4):1091-1105
pubmed: 28254829
Nat Methods. 2007 Jul;4(7):559-61
pubmed: 17558414
J Neurosci. 2007 Nov 7;27(45):12255-66
pubmed: 17989291
Curr Opin Neurol. 2015 Dec;28(6):556-64
pubmed: 26402408
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6536-41
pubmed: 16617114
Nature. 2011 Jun 19;476(7360):341-5
pubmed: 21685886
Nature. 2016 Jan 28;529(7587):528-31
pubmed: 26789249
J Neurosci. 2012 Oct 17;32(42):14489-510
pubmed: 23077035
Blood. 2008 Apr 1;111(7):3498-506
pubmed: 18195090
Diabetes. 2016 Dec;65(12):3552-3560
pubmed: 27613809
Cell. 2019 Dec 12;179(7):1483-1498.e22
pubmed: 31813625
J Neurosci. 2017 Apr 19;37(16):4231-4242
pubmed: 28314814
PLoS One. 2011;6(11):e27385
pubmed: 22110636
J Cell Biol. 2006 Sep 25;174(7):915-21
pubmed: 16982799
Sci Signal. 2012 Jul 03;5(231):ra47
pubmed: 22763339
Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12937-42
pubmed: 21768369
Neuron. 2007 Mar 1;53(5):639-47
pubmed: 17329205