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Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling.
Cell Metabolism ( IF 27.7 ) Pub Date : 2020-03-26 , DOI: 10.1016/j.cmet.2020.03.005 Jana Gӧbel 1 , Esther Engelhardt 1 , Patric Pelzer 1 , Vignesh Sakthivelu 1 , Hannah M Jahn 1 , Milica Jevtic 1 , Kat Folz-Donahue 2 , Christian Kukat 2 , Astrid Schauss 1 , Christian K Frese 1 , Patrick Giavalisco 2 , Alexander Ghanem 3 , Karl-Klaus Conzelmann 3 , Elisa Motori 2 , Matteo Bergami 4
Cell Metabolism ( IF 27.7 ) Pub Date : 2020-03-26 , DOI: 10.1016/j.cmet.2020.03.005 Jana Gӧbel 1 , Esther Engelhardt 1 , Patric Pelzer 1 , Vignesh Sakthivelu 1 , Hannah M Jahn 1 , Milica Jevtic 1 , Kat Folz-Donahue 2 , Christian Kukat 2 , Astrid Schauss 1 , Christian K Frese 1 , Patrick Giavalisco 2 , Alexander Ghanem 3 , Karl-Klaus Conzelmann 3 , Elisa Motori 2 , Matteo Bergami 4
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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.
中文翻译：
反应性星形胶质细胞中的线粒体-内质网接触促进血管重塑。
星形胶质细胞在脑组织修复中发挥着重要作用。然而，其潜在机制仍然知之甚少。我们表明，急性损伤和血脑屏障破坏会触发星形胶质细胞尾足中突出的富含线粒体的隔室的形成，这使得血管重塑成为可能。综合成像方法表明，这种线粒体聚类是由融合动力学调节的适应性反应的一部分。Mitofusin 2 (Mfn2) 的星形胶质细胞特异性条件缺失抑制血管周围线粒体聚集并破坏线粒体-内质网 (ER) 接触位点。从功能上讲，双光子成像实验表明，这些结构变化反映在线粒体 Ca2+ 摄取受损导致体内尾足内异常的细胞溶质瞬变中。在组织水平上，通过增强 MFN2 缺陷星形胶质细胞中的线粒体-ER 血管周围束缚，恢复了受损区域受损的血管复杂性。这些数据揭示了线粒体动力学在协调星形胶质细胞局部域中的关键作用，并对修复受伤的大脑具有重要意义。
更新日期：2020-04-20
中文翻译：
反应性星形胶质细胞中的线粒体-内质网接触促进血管重塑。
星形胶质细胞在脑组织修复中发挥着重要作用。然而，其潜在机制仍然知之甚少。我们表明，急性损伤和血脑屏障破坏会触发星形胶质细胞尾足中突出的富含线粒体的隔室的形成，这使得血管重塑成为可能。综合成像方法表明，这种线粒体聚类是由融合动力学调节的适应性反应的一部分。Mitofusin 2 (Mfn2) 的星形胶质细胞特异性条件缺失抑制血管周围线粒体聚集并破坏线粒体-内质网 (ER) 接触位点。从功能上讲，双光子成像实验表明，这些结构变化反映在线粒体 Ca2+ 摄取受损导致体内尾足内异常的细胞溶质瞬变中。在组织水平上，通过增强 MFN2 缺陷星形胶质细胞中的线粒体-ER 血管周围束缚，恢复了受损区域受损的血管复杂性。这些数据揭示了线粒体动力学在协调星形胶质细胞局部域中的关键作用，并对修复受伤的大脑具有重要意义。
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