Inserm, U1127, F-75013, Paris, France; CNRS, UMR 7225, F-75013, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013, Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.
Inserm, U1127, F-75013, Paris, France; CNRS, UMR 7225, F-75013, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013, Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.
Neurochem Int. 2017 Oct;109:171-183. doi: 10.1016/j.neuint.2017.03.021. Epub 2017 Apr 5.
Over the last years, contact sites between the endoplasmic reticulum (ER) and mitochondria have attracted great attention in the study of cell homeostasis and dysfunction, especially in the context of neurodegenerative disorders. This is largely due to the critical involvement of this subcellular compartment in a plethora of vital cellular functions: Ca homeostasis, mitochondrial dynamics, transport, bioenergetics and turnover, ER stress, apoptotic signaling and inflammation. An increasing number of disease-associated proteins have been reported to physically associate with the ER-mitochondria interface, and cause structural and/or functional perturbations of this compartment. In the present review, we summarize current knowledge about the architecture and functions of the ER-mitochondria contact sites, and the consequences of their alteration in different neurodegenerative disorders. Special emphasis is placed on the caveats and difficulties in defining the nature and origin of the highlighted defects in ER-mitochondria communication, and their exact contribution to the neurodegenerative process.
在过去的几年中，内质网 (ER) 和线粒体之间的接触位点在细胞内稳态和功能障碍的研究中引起了极大的关注，尤其是在神经退行性疾病的背景下。这在很大程度上是由于这个亚细胞区室在许多重要的细胞功能中具有关键作用：Ca 稳态、线粒体动力学、运输、生物能学和周转率、内质网应激、凋亡信号和炎症。越来越多的与疾病相关的蛋白质已被报道与 ER-线粒体界面发生物理关联，并导致该区域的结构和/或功能发生改变。在本综述中，我们总结了 ER-线粒体接触位点的结构和功能的最新知识，以及它们在不同神经退行性疾病中的改变所带来的后果。特别强调了在定义 ER-线粒体通讯中突出缺陷的性质和起源以及它们对神经退行性过程的确切贡献方面存在的困难和注意事项。
