Liu Jinxuan, Yang Jinghua
Department of Toxicology, School of Public Health, China Medical University, NO.77 Puhe road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
Biomed Pharmacother. 2022 May;149:112890. doi: 10.1016/j.biopha.2022.112890. Epub 2022 Mar 31.
In eukaryotic cells, organelles could coordinate complex mechanisms of signaling transduction metabolism and gene expression through their functional interactions. The functional domain between ER and mitochondria, called mitochondria-associated membranes (MAM), is closely associated with various physiological functions including intracellular lipid transport, Ca transfer, mitochondria function maintenance, and autophagosome formation. In addition, more evidence suggests that MAM modulate cellular functions in health and disease. Studies have also demonstrated the association of MAM with numerous diseases, including neurodegenerative diseases, cancer, viral infection, obesity, and diabetes. In fact, recent evidence revealed a close relationship of MAM with Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases. In this view, elucidating the role of MAM in neurodegenerative diseases is particularly important. This review will focus the main tethering protein complexes of MAM and functions of MAM. Besides, the role of MAM in the regulation of neurodegenerative diseases and the potential molecular mechanisms is introduced to provide a new understanding of the pathogenesis of these diseases.
在真核细胞中，细胞器可通过其功能相互作用来协调信号转导、代谢和基因表达的复杂机制。内质网（ER）和线粒体之间的功能结构域，称为线粒体相关膜（MAM），它与多种生理功能密切相关，包括细胞内脂质转运、钙转运、线粒体功能维持和自噬体形成。此外，越来越多的证据表明，MAM在健康和疾病状态下调节细胞功能。研究还表明，MAM与多种疾病有关，包括神经退行性疾病、癌症、病毒感染、肥胖症和糖尿病。事实上，最近的证据揭示了MAM与阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿舞蹈病（HD）、肌萎缩侧索硬化症（ALS）及其他神经退行性疾病之间存在密切关系。从这个角度来看，阐明MAM在神经退行性疾病中的作用尤为重要。本综述将聚焦于MAM的主要锚定蛋白复合物及其功能。此外，还介绍了MAM在神经退行性疾病调控中的作用及潜在分子机制，以期为这些疾病的发病机制提供新的认识。
