Laboratory for Technologies of Advanced Therapies, Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Italy.
Adv Exp Med Biol. 2012;740:411-37. doi: 10.1007/978-94-007-2888-2_17.
The tight interplay between endoplasmic reticulum (ER) and mitochondria is a key determinant of cell function and survival through the control of intracellular calcium (Ca(2+)) signaling. The specific sites of physical association between ER and mitochondria are known as mitochondria-associated membranes (MAMs). It has recently become clear that MAMs are crucial for highly efficient transmission of Ca(2+) from the ER to mitochondria, thus controlling fundamental processes involved in energy production and also determining cell fate by triggering or preventing apoptosis. In this contribution, we summarize the main features of the Ca(2+)-signaling toolkit, covering also the latest breakthroughs in the field, such as the identification of novel candidate proteins implicated in mitochondrial Ca(2+) transport and the recent direct characterization of the high-Ca(2+) microdomains between ER and mitochondria. We review the main functions of these two organelles, with special emphasis on Ca(2+) handling and on the structural and molecular foundations of the signaling contacts between them. Additionally, we provide important examples of the physiopathological role of this cross-talk, briefly describing the key role played by MAMs proteins in many diseases, and shedding light on the essential role of mitochondria-ER interactions in the maintenance of cellular homeostasis and the determination of cell fate.
内质网（ER）和线粒体之间的紧密相互作用是通过控制细胞内钙离子（Ca(2+)）信号来决定细胞功能和存活的关键决定因素。内质网和线粒体之间物理结合的特定部位称为线粒体相关膜（MAMs）。最近已经清楚，MAMs 对于从 ER 到线粒体的 Ca(2+)的高效传递至关重要，从而控制与能量产生相关的基本过程，并通过触发或防止细胞凋亡来决定细胞命运。在这篇综述中，我们总结了 Ca(2+)信号工具箱的主要特征，包括该领域的最新突破，例如鉴定涉及线粒体 Ca(2+)转运的新候选蛋白，以及最近对 ER 和线粒体之间的高 Ca(2+)微区的直接特征描述。我们回顾了这两个细胞器的主要功能，特别强调 Ca(2+)处理以及它们之间信号联系的结构和分子基础。此外，我们提供了这种串扰的生理病理学作用的重要实例，简要描述了 MAMs 蛋白在许多疾病中发挥的关键作用，并阐明了线粒体-ER 相互作用在维持细胞内稳态和决定细胞命运中的重要作用。
