Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
Maria Cecilia Hospital, GVM Care & Research, Cotignola (RA), Italy.
Int Rev Cell Mol Biol. 2020;350:119-196. doi: 10.1016/bs.ircmb.2019.11.002. Epub 2019 Dec 3.
Mitochondria and endoplasmic reticulum (ER) are fundamental in the control of cell physiology regulating several signal transduction pathways. They continuously communicate exchanging messages in their contact sites called MAMs (mitochondria-associated membranes). MAMs are specific microdomains acting as a platform for the sorting of vital and dangerous signals. In recent years increasing evidence reported that multiple scaffold proteins and regulatory factors localize to this subcellular fraction suggesting MAMs as hotspot signaling domains. In this review we describe the current knowledge about MAMs' dynamics and processes, which provided new correlations between MAMs' dysfunctions and human diseases. In fact, MAMs machinery is strictly connected with several pathologies, like neurodegeneration, diabetes and mainly cancer. These pathological events are characterized by alterations in the normal communication between ER and mitochondria, leading to deep metabolic defects that contribute to the progression of the diseases.
线粒体和内质网（ER）在控制细胞生理学中起着重要作用，调节着几种信号转导途径。它们通过在称为 MAMs（线粒体相关膜）的接触位点不断交换信息来进行持续的通讯。MAMs 是特定的微区，作为重要和危险信号分拣的平台。近年来，越来越多的证据表明，多种支架蛋白和调节因子定位于这个亚细胞区室，提示 MAMs 是信号热点域。在这篇综述中，我们描述了关于 MAMs 动力学和过程的最新知识，这些知识为 MAMs 功能障碍与人类疾病之间的新关联提供了依据。事实上，MAMs 机制与多种病理学密切相关，如神经退行性疾病、糖尿病，主要还有癌症。这些病理事件的特征是 ER 和线粒体之间正常通讯的改变，导致严重的代谢缺陷，从而促进疾病的进展。
