线粒体相关的内质网膜（MAMs）与疾病发病机制中Ca2+转运的相关性
The correlation between mitochondria-associated endoplasmic reticulum membranes (MAMs) and Ca2+ transport in the pathogenesis of diseases
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影响因子:8.4
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
DOI:
10.1038/s41401-024-01359-9
摘要
线粒体和内质网（ER）是影响多种细胞生理和病理过程的重要细胞器。最新研究表明，线粒体外膜的约5%-20%能与ER形成高度动态的物理连接，保持在10-30纳米的距离内。这些称为MAMs的相互连接，是真核细胞中相对保守的结构，作为线粒体与ER之间物质交换的关键平台，以维持细胞的多方面稳态。特别是，ER介导的Ca2+释放及回收与MAMs的结构和功能密切相关。因此，MAMs在细胞内Ca2+转运和Ca2+稳态的维持中起核心作用，参与代谢调控、信号转导、自噬和凋亡等多种细胞活动。某些疾病状态下，如心血管疾病、神经退行性疾病及癌症中观察到的MAMs破坏，会导致Ca2+稳态失衡，可能加重病理变化和疾病进展。因此，深入理解MAMs介导的Ca2+转运与这些疾病的关系，有望揭示新的治疗视角和策略。本文综述了疾病进展过程中MAMs功能的变化及其与MAMs相关的Ca2+转运的关系。
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.