Endoplasmic reticulum-mitochondria contacts: molecular hubs for neuronal regulation

线粒体是所有有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。线粒体利用微管作为轨道，沿着神经元突起移动，为最远的部位提供能量。线粒体与内质网（ER）膜相结合，以发挥其功能。我假设内质网的特殊位点作为线粒体定位的调节器，并参与建立适当的神经元形态。我的这一假设基于先前的证据，即钙是线粒体对接的调节因子之一，er -线粒体接触位点是钙交换的热点。综上所述，这表明内质网是捕获神经元特定部位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内质网线粒体接触的定位。此外，由于线粒体与分支模式和神经元发育有关，我将描述线粒体定位改变后的神经元形态。最后，我将利用一种神经退行性疾病的小鼠模型，探讨er -线粒体接触改变对神经元死亡和存活的影响。

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.