Leal Nuno Santos, Martins Luís Miguel
MRC Toxicology Unit, University of Cambridge, Cambridge CB2 1QR, UK.
Biomedicines. 2021 Feb 23;9(2):227. doi: 10.3390/biomedicines9020227.
The way organelles are viewed by cell biologists is quickly changing. For many years, these cellular entities were thought to be unique and singular structures that performed specific roles. However, in recent decades, researchers have discovered that organelles are dynamic and form physical contacts. In addition, organelle interactions modulate several vital biological functions, and the dysregulation of these contacts is involved in cell dysfunction and different pathologies, including neurodegenerative diseases. Mitochondria-ER contact sites (MERCS) are among the most extensively studied and understood juxtapositioned interorganelle structures. In this review, we summarise the major biological and ultrastructural dysfunctions of MERCS in neurodegeneration, with a particular focus on Alzheimer's disease as well as Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. We also propose an updated version of the MERCS hypothesis in Alzheimer's disease based on new findings. Finally, we discuss the possibility of MERCS being used as possible drug targets to halt cell death and neurodegeneration.
细胞生物学家观察细胞器的方式正在迅速改变。多年来，这些细胞实体被认为是具有特定功能的独特单一结构。然而，近几十年来，研究人员发现细胞器是动态的，并且会形成物理接触。此外，细胞器间的相互作用调节着多种重要的生物学功能，而这些接触的失调与细胞功能障碍和包括神经退行性疾病在内的不同病理状态有关。线粒体-内质网接触位点（MERCS）是研究最为广泛且了解最多的并列细胞器间结构之一。在本综述中，我们总结了MERCS在神经退行性变中的主要生物学和超微结构功能障碍，特别关注阿尔茨海默病以及帕金森病、肌萎缩侧索硬化症和额颞叶痴呆。我们还基于新发现提出了阿尔茨海默病中MERCS假说的更新版本。最后，我们讨论了将MERCS用作阻止细胞死亡和神经退行性变的潜在药物靶点的可能性。
