Department of Cardiology, Zhongshan Hospital, Fudan University; Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
Cell Death Dis. 2022 May 27;13(5):504. doi: 10.1038/s41419-022-04942-2.
The endoplasmic reticulum (ER) and mitochondria are interconnected intracellular organelles with vital roles in the regulation of cell signaling and function. While the ER participates in a number of biological processes including lipid biosynthesis, Ca storage and protein folding and processing, mitochondria are highly dynamic organelles governing ATP synthesis, free radical production, innate immunity and apoptosis. Interplay between the ER and mitochondria plays a crucial role in regulating energy metabolism and cell fate control under stress. The mitochondria-associated membranes (MAMs) denote physical contact sites between ER and mitochondria that mediate bidirectional communications between the two organelles. Although Ca transport from ER to mitochondria is vital for mitochondrial homeostasis and energy metabolism, unrestrained Ca transfer may result in mitochondrial Ca overload, mitochondrial damage and cell death. Here we summarize the roles of MAMs in cell physiology and its impact in pathological conditions with a focus on cardiovascular disease. The possibility of manipulating ER-mitochondria contacts as potential therapeutic approaches is also discussed.
内质网（ER）和线粒体是相互联系的细胞内细胞器，在细胞信号转导和功能调节中起着至关重要的作用。虽然内质网参与了许多生物学过程，包括脂质生物合成、Ca 储存和蛋白质折叠和加工，但线粒体是高度动态的细胞器，负责 ATP 合成、自由基产生、先天免疫和细胞凋亡。内质网和线粒体之间的相互作用在应激下调节能量代谢和细胞命运控制中起着关键作用。线粒体相关膜（MAMs）表示 ER 和线粒体之间的物理接触位点，介导两个细胞器之间的双向通讯。虽然 ER 向线粒体的 Ca 转运对于线粒体的稳态和能量代谢至关重要，但无限制的 Ca 转移可能导致线粒体 Ca 超载、线粒体损伤和细胞死亡。在这里，我们总结了 MAMs 在细胞生理学中的作用及其在病理条件下的影响，重点是心血管疾病。还讨论了操纵 ER-线粒体接触作为潜在治疗方法的可能性。
