Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) serve as essential hubs for interorganelle communication in eukaryotic cells and play multifunctional roles in various biological pathways. A defect in ER-mitochondria signaling or MAMs dysfunction has pleiotropic effects on a variety of intracellular events, which results in disturbances of the mitochondrial quality control system, Ca²⁺ dyshomeostasis, apoptosis, ER stress, and inflammasome activation, which all contribute to the onset and progression of kidney disease. Here, we review the structure and molecular compositions of MAMs as well as the experimental methods used to study these interorganellar contact sites. We will specifically summarize the downstream signaling pathways regulated by MAMs, mainly focusing on mitochondrial quality control, oxidative stress, ER-mitochondria Ca²⁺ crosstalk, apoptosis, inflammasome activation, and ER stress. Finally, we will discuss how alterations in MAMs integrity contribute to the pathogenesis of kidney disease and offer directions for future research.

中文翻译：

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线粒体相关内质网膜 (MAM) 及其在肾脏疾病中的前瞻性作用。


线粒体相关内质网（ER）膜（MAM）是真核细胞细胞器间通讯的重要枢纽，并在各种生物途径中发挥多功能作用。 ER-线粒体信号传导缺陷或 MAM 功能障碍对多种细胞内事件具有多效性影响，导致线粒体质量控制系统紊乱、Ca ²⁺稳态失衡、细胞凋亡、ER 应激和炎症小体激活，这些都有助于肾脏疾病的发生和进展。在这里，我们回顾了 MAM 的结构和分子组成以及用于研究这些细胞间接触位点的实验方法。我们将具体总结MAMs调控的下游信号通路，主要集中在线粒体质量控制、氧化应激、ER-线粒体Ca ²⁺串扰、细胞凋亡、炎症小体激活和ER应激等方面。最后，我们将讨论 MAM 完整性的改变如何影响肾脏疾病的发病机制，并为未来的研究提供方向。