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，大约 5%-20% 的线粒体外膜能够与 ER 形成高度动态的物理连接，保持在 10-30 nm 的距离。这些相互连接，称为 MAM，代表真核细胞中相对保守的结构，充当线粒体和 ER 之间物质交换的关键平台，以维持细胞稳态的各个方面。特别是，ER 介导的 Ca2 释放和再循环与 MAM 的结构和功能密切相关。因此，MAM 在细胞内 Ca2+ 转运和 Ca2+ 稳态维持中不可或缺，在代谢调节、信号转导、自噬和凋亡等多种细胞活动中发挥着重要作用。在心血管和神经退行性疾病以及癌症等某些病理学中观察到的 MAM 破坏会导致 Ca2 稳态紊乱。这种不平衡可能会加剧病理改变和疾病进展。因此，彻底了解 MAM 介导的 Ca2 转运与这些疾病之间的联系可以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 MAM 功能的变化及其对 MAM 相关 Ca2 转运的影响。© 2024。作者获得中国科学院上海药物研究所和中国药理学会的独家许可社会。

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 Ca2+ release and recycling are intricately associated with the structure and functionality of MAMs. Thus, MAMs are integral in intracellular Ca2+ transport and the maintenance of Ca2+ 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 Ca2+ homeostasis. This imbalance potentially aggravates pathological alterations and disease progression. Consequently, a thorough understanding of the link between MAM-mediated Ca2+ 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 Ca2+ transport.© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.