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Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling.

Authors
  • Gӧbel, Jana1
  • Engelhardt, Esther1
  • Pelzer, Patric1
  • Sakthivelu, Vignesh1
  • Jahn, Hannah M1
  • Jevtic, Milica1
  • Folz-Donahue, Kat2
  • Kukat, Christian2
  • Schauss, Astrid1
  • Frese, Christian K1
  • Giavalisco, Patrick2
  • Ghanem, Alexander3
  • Conzelmann, Karl-Klaus3
  • Motori, Elisa4
  • Bergami, Matteo5
  • 1 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne and University Hospital Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany. , (Germany)
  • 2 Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany. , (Germany)
  • 3 Max von Pettenkofer-Institute Virology, Faculty of Medicine and Gene Center, Ludwig Maximilians University Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany. , (Germany)
  • 4 Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany. Electronic address: [email protected] , (Germany)
  • 5 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne and University Hospital Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Institute of Genetics, University of Cologne, Zülpicher Str. 47a, 50674 Cologne, Germany; Center for Molecular Medicine, Robert-Koch-Str. 21, 50931 Cologne, Germany. Electronic address: [email protected] , (Germany)
Type
Published Article
Journal
Cell metabolism
Publication Date
Apr 07, 2020
Volume
31
Issue
4
Identifiers
DOI: 10.1016/j.cmet.2020.03.005
PMID: 32220306
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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 Ca2+ uptake leading to abnormal cytosolic transients within endfeet in vivo. At the tissue level, a compromised vascular complexity in the lesioned area was restored by boosting mitochondrial-ER perivascular tethering in MFN2-deficient astrocytes. These data unmask a crucial role for mitochondrial dynamics in coordinating astrocytic local domains and have important implications for repairing the injured brain. Copyright © 2020 Elsevier Inc. All rights reserved.

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