Endoplasmic reticulum-mitochondria contacts: molecular hubs for neuronal regulation

内质网-线粒体接触：神经元调节的分子中枢

• 批准号: 286590665
• 负责人: Dr. Gabriela Plucinska
• 金额: --
• 依托单位: Cell Biology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/286590665?language=en
• 关键词: Endoplasmic; reticulum; mitochondria; contacts; molecular

Mitochondria are vital organelles for all aerobic cells. Neurons, due to their complex morphology, are particularly dependent on the proper distribution of mitochondria. Using microtubules as tracks, mitochondria move along neuronal projections to provide energy to the most distal sites. To perform their function properly mitochondria associate with endoplasmic reticulum (ER) membranes. I hypothesize that specialized sites of the ER act as regulators of mitochondrial localization and are involved in establishing proper neuronal morphology. I base this hypothesis on previous evidence that calcium is one of the regulators of mitochondrial docking and the fact that ER-mitochondria contact sites are the hotspots of calcium exchange. Together this suggests that the ER is part of the machinery that captures mitochondria at specific sites in neurons. I propose a set of experiments using an ex vivo approach to visualize and manipulate the localization of ER-mitochondria contacts. Further, as mitochondria are implicated in branching patterns and neuronal development I will characterize neuronal morphology upon altered mitochondrial localization. Finally I will explore the impact of altered ER-mitochondria contacts on neuronal death and survival using one of the mouse models of neurodegenerative diseases.

线粒体是所有需氧细胞的重要细胞器。神经元由于其复杂的形态，特别依赖于线粒体的适当分布。利用微管作为轨道，线粒体沿着神经元投射移动，为最远端的部位提供能量。为了正常发挥功能，线粒体与内质网（ER）膜相连。我推测，专门网站的ER作为监管机构的线粒体定位，并参与建立适当的神经元形态。我的这一假设的基础上以前的证据表明，钙是线粒体对接的监管机构之一，事实上，ER-线粒体接触网站是钙交换的热点。总之，这表明ER是在神经元的特定部位捕获线粒体的机制的一部分。我提出了一组实验，使用离体方法来可视化和操纵ER-线粒体接触的本地化。此外，由于线粒体与分支模式和神经元发育有关，我将在改变线粒体定位后表征神经元形态。最后，我将探讨改变ER线粒体接触神经元死亡和生存的影响，使用神经退行性疾病的小鼠模型之一。