Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling

Göbel, Jana; Engelhardt, Esther; Pelzer, Patric; Sakthivelu, Vignesh; Jahn, Hannah M.; Jevtic, Milica; Folz-Donahue, Kat; Kukat, Christian; Schauss, Astrid; Frese, Christian K.; Giavalisco, Patrick; Ghanem, Alexander; Conzelmann, Karl-Klaus; Motori, Elisa und Bergami, Matteo (2020): Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling. In: Cell Metabolism, Bd. 31, Nr. 4: S. 791-808

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1550-4131
• Sprache: Englisch