线粒体相关的内质网膜（MAM）与Ca2转运在疾病发病机理中的相关性
The correlation between mitochondria-associated endoplasmic reticulum membranes (MAMs) and Ca2+ transport in the pathogenesis of diseases
影响因子:8.40000
分区:医学2区 / 药学1区 化学：综合2区
发表日期:2025 Feb
作者:
Wen-Bin Zhao, Rui Sheng
摘要
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，线粒体外膜的约5％-20％能够与ER形成高度动态的物理联系，保持在10-30 nm的距离。这些被称为MAM的互连代表了真核细胞中相对保守的结构，它是线粒体和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释放和回收与MAM的结构和功能相关。因此，MAM在细胞内CA2转运和CA2稳态的维持中是不可或缺的，在各种细胞活性中起着至关重要的作用，包括代谢调节，信号转导，自噬和凋亡。在某些病理中观察到的妈妈的破坏，例如心血管和神经退行性疾病以及癌症导致CA2稳态的扰动。这种失衡可能会加剧病理改变和疾病进展。因此，对MAM介导的CA2运输与这些疾病之间的联系有透彻的了解可以揭示新的观点和治疗策略。这篇综述着重于疾病进展过程中MAMS功能的变化及其与MAM相关的CA2转运的影响。
Abstract
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.