Goebel, Jana, Engelhardt, Esther, Pelzer, Patric, Sakthivelu, Vignesh, Jahn, Hannah M., Jevtic, Milica, Folz-Donahue, Kat, Kukat, Christian ORCID: 0000-0003-1508-0229, Schauss, Astrid, Frese, Christian K., Giavalisco, Patrick, Ghanem, Alexander, Conzelmann, Karl-Klaus ORCID: 0000-0002-8614-3656, Motori, Elisa and Bergami, Matteo ORCID: 0000-0001-5525-5025 (2020). Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling. Cell Metab., 31 (4). S. 791 - 817. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Goebel, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engelhardt, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pelzer, PatricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sakthivelu, VigneshUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jahn, Hannah M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jevtic, MilicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Folz-Donahue, KatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kukat, ChristianUNSPECIFIEDorcid.org/0000-0003-1508-0229UNSPECIFIED
Schauss, AstridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frese, Christian K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giavalisco, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ghanem, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Conzelmann, Karl-KlausUNSPECIFIEDorcid.org/0000-0002-8614-3656UNSPECIFIED
Motori, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergami, MatteoUNSPECIFIEDorcid.org/0000-0001-5525-5025UNSPECIFIED
URN: urn:nbn:de:hbz:38-337463
DOI: 10.1016/j.cmet.2020.03.005
Journal or Publication Title: Cell Metab.
Volume: 31
Number: 4
Page Range: S. 791 - 817
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MITOFUSIN 2; AXONAL-TRANSPORT; RABIES VIRUS; DYNAMICS; FUSION; METABOLISM; PROTECTS; NEURONS; CELLS; MOUSEMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33746

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