反應性星形膠質細胞中的線粒體-內質網接觸促進血管重塑
作者：
小柯機器人發布時間：2020/3/28 21:50:52
德國科隆大學Matteo Bergami、馬克斯普朗克衰老生物學研究所 Elisa Motori等研究人員合作發現，反應性星形膠質細胞中的線粒體-內質網接觸促進血管重塑。這一研究成果於2020年3月26日在線發表在國際學術期刊《細胞—代謝》上。
研究人員發現，急性損傷和血腦屏障破壞觸發星形膠質細胞尾端的線粒體富集區室形成，從而使血管重塑。綜合成像方法表明，這種線粒體聚集是融合動態調節的自適應反應中的一部分。星形膠質細胞中條件性敲除線粒體融合素2（Mfn2）能夠抑制血管周圍線粒體聚集並破壞線粒體-內質網（ER）接觸位點。
從功能上講，兩光子成像實驗表明，這些結構變化被線粒體Ca2+吸收受損所反映，從而導致體內尾端異常的胞質改變。在組織水平上，通過加強MFN2缺失星形膠質細胞中線粒體-ER血管周圍束縛，可以恢復病變區域受損的血管複雜性。這些數據揭示了線粒體動態在協調星形細胞局部區域中的關鍵作用，並對大腦損傷修復具有重要意義。
據悉，星形膠質細胞在腦組織修復中起著重要作用。但是，其背後的機制仍然知之甚少。
附：英文原文
Title: Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling
Author: Jana Gbel, Esther Engelhardt, Patric Pelzer, Vignesh Sakthivelu, Hannah M. Jahn, Milica Jevtic, Kat Folz-Donahue, Christian Kukat, Astrid Schauss, Christian K. Frese, Patrick Giavalisco, Alexander Ghanem, Karl-Klaus Conzelmann, Elisa Motori, Matteo Bergami
Issue&Volume: 2020-03-26
Abstract: Astrocytes have emerged for playing important roles in brain tissue repair; however,the underlying mechanisms remain poorly understood. We show that acute injury andblood-brain barrier disruption trigger the formation of a prominent mitochondrial-enrichedcompartment in astrocytic endfeet, which enables vascular remodeling. Integrated imagingapproaches revealed that this mitochondrial clustering is part of an adaptive responseregulated by fusion dynamics. Astrocyte-specific conditional deletion of Mitofusin2 (Mfn2) suppressed perivascular mitochondrial clustering and disrupted mitochondria-endoplasmicreticulum (ER) contact sites. Functionally, two-photon imaging experiments showedthat 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 wasrestored by boosting mitochondrial-ER perivascular tethering in MFN2-deficient astrocytes.These data unmask a crucial role for mitochondrial dynamics in coordinating astrocyticlocal domains and have important implications for repairing the injured brain.
DOI: 10.1016/j.cmet.2020.03.005
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30120-0