Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35121 Padua, Italy.
Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35121 Padua, Italy; Neuroscience Institute - Italian National Research Council (CNR), Padua, 35121, Italy.
Pharmacol Res. 2018 Feb;128:42-51. doi: 10.1016/j.phrs.2018.01.003. Epub 2018 Jan 5.
The endoplasmic reticulum (ER) and the mitochondrial network are two highly interconnected cellular structures. By proteinaceous tethers, specialized membrane domains of the ER are tightly associated with the outer membrane of mitochondria, allowing the assembly of signaling platforms where different cell functions take place or are modulated, such as lipid biosynthesis, Ca homeostasis, inflammation, autophagy and apoptosis. The ER-mitochondria coupling is highly dynamic and contacts between the two organelles can be modified in their number, extension and thickness by different stimuli. Importantly, several pathological conditions, such as cancer, neurodegenerative diseases and metabolic syndromes show alterations in this feature, underlining the key role of ER-mitochondria crosstalk in cell physiology. In this contribution, we will focus on one of the major modulator of ER-mitochondria apposition, Mitofusin 2, discussing the structure of the protein and its debated role on organelles tethering. Moreover, we will critically describe different techniques commonly used to investigate this crucial issue, highlighting their advantages, drawbacks and limits.
内质网（ER）和线粒体网络是两个高度相互关联的细胞结构。通过蛋白质丝，内质网的特殊膜域与线粒体的外膜紧密相连，允许组装信号平台，在这些平台上发生或调节不同的细胞功能，如脂质生物合成、Ca 稳态、炎症、自噬和细胞凋亡。ER-线粒体的偶联是高度动态的，两个细胞器之间的接触可以通过不同的刺激来改变其数量、延伸和厚度。重要的是，几种病理状况，如癌症、神经退行性疾病和代谢综合征，在这种特征上表现出改变，这突显了 ER-线粒体串扰在细胞生理学中的关键作用。在这篇文章中，我们将集中讨论内质网-线粒体贴附的主要调节剂之一——线粒体融合蛋白 2，讨论该蛋白的结构及其在细胞器连接中的有争议的作用。此外，我们还将批判性地描述常用于研究这一关键问题的不同技术，突出它们的优点、缺点和局限性。
