Zhao Wen-Bin, Sheng Rui
Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences of Soochow University, Suzhou, 215123, China.
Acta Pharmacol Sin. 2025 Feb;46(2):271-291. doi: 10.1038/s41401-024-01359-9. Epub 2024 Aug 8.
Mitochondria and the endoplasmic reticulum (ER) are vital organelles that influence various cellular physiological and pathological processes. Recent evidence shows that about 5%-20% of the mitochondrial outer membrane is capable of forming a highly dynamic physical connection with the ER, maintained at a distance of 10-30 nm. These interconnections, known as MAMs, represent a relatively conserved structure in eukaryotic cells, acting as a critical platform for material exchange between mitochondria and the ER to maintain various aspects of cellular homeostasis. Particularly, ER-mediated Ca release and recycling are intricately associated with the structure and functionality of MAMs. Thus, MAMs are integral in intracellular Ca transport and the maintenance of Ca homeostasis, playing an essential role in various cellular activities including metabolic regulation, signal transduction, autophagy, and apoptosis. The disruption of MAMs observed in certain pathologies such as cardiovascular and neurodegenerative diseases as well as cancers leads to a disturbance in Ca homeostasis. This imbalance potentially aggravates pathological alterations and disease progression. Consequently, a thorough understanding of the link between MAM-mediated Ca transport and these diseases could unveil new perspectives and therapeutic strategies. This review focuses on the changes in MAMs function during disease progression and their implications in relation to MAM-associated Ca transport.
线粒体和内质网（ER）是影响各种细胞生理和病理过程的重要细胞器。最近的证据表明，约5%-20%的线粒体外膜能够与内质网形成高度动态的物理连接，两者间距保持在10-30纳米。这些相互连接被称为线粒体相关内质网膜（MAMs），是真核细胞中相对保守的结构，作为线粒体和内质网之间物质交换的关键平台，以维持细胞内稳态的各个方面。特别地，内质网介导的钙释放和再循环与线粒体相关内质网膜的结构和功能密切相关。因此，线粒体相关内质网膜在细胞内钙运输和钙稳态维持中不可或缺，在包括代谢调节、信号转导、自噬和细胞凋亡在内的各种细胞活动中发挥着重要作用。在某些病理学情况如心血管疾病、神经退行性疾病以及癌症中观察到的线粒体相关内质网膜的破坏会导致钙稳态紊乱。这种失衡可能会加剧病理改变和疾病进展。因此，深入了解线粒体相关内质网膜介导的钙运输与这些疾病之间的联系可能会揭示新的观点和治疗策略。本综述重点关注疾病进展过程中线粒体相关内质网膜功能的变化及其与线粒体相关内质网膜相关钙运输的关系。
