Organelles juxtaposition has been detected for decades, although only recently gained importance due to a pivotal role in the regulation of cellular processes dependent on membrane contact sites. Endoplasmic reticulum (ER) and mitochondria interaction is a prime example of organelles contact sites. Mitochondria-associated membranes (MAM) are proposed to harbor ER-mitochondria tether complexes, mainly when these organelles are less than 30 nm apart. Dysfunctions of proteins located at the MAM are associated with neurodegenerative diseases such as Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis, as well as neurodevelopmental disorders; hence any malfunction in MAM can potentially trigger cell death. This review will focus on the role of ER-mitochondria contact sites, regarding calcium homeostasis, lipid metabolism, autophagy, morphology and dynamics of mitochondria, mainly in the context of neurodegenerative diseases. Approaches that have been employed so far to study organelles contact sites, as well as methods that were not used in neurosciences yet, but are promising and accurate ways to unveil the functions of MAM during neurodegeneration, is also discussed in the present review.

几十年来已经检测到细胞器并置，尽管由于在调节依赖于膜接触位点的细胞过程中的关键作用直到最近才变得重要。内质网 (ER) 和线粒体相互作用是细胞器接触位点的主要例子。线粒体相关膜 (MAM) 被提议含有 ER-线粒体系链复合物，主要是当这些细胞器相距小于 30 nm 时。位于 MAM 的蛋白质功能障碍与神经退行性疾病有关，例如帕金森氏症、阿尔茨海默氏症和肌萎缩性侧索硬化症，以及神经发育障碍；因此，MAM 中的任何故障都可能引发细胞死亡。本综述将重点关注 ER-线粒体接触部位的作用，包括钙稳态、脂质代谢、自噬、线粒体的形态和动力学，主要是在神经退行性疾病的背景下。本综述还讨论了迄今为止用于研究细胞器接触位点的方法，以及尚未在神经科学中使用但有希望且准确的方法来揭示 MAM 在神经退行性变期间的功能的方法。