Center for Geroscience, Brain Health and Metabolism, Faculty of Medicine, University of Chile, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Center for Geroscience, Brain Health and Metabolism, Faculty of Medicine, University of Chile, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA, 94945, USA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Cell Calcium. 2018 Mar;70:24-31. doi: 10.1016/j.ceca.2017.08.004. Epub 2017 Aug 20.
Endoplasmic reticulum (ER) calcium signaling is implicated in a myriad of coordinated cellular processes. The ER calcium content is tightly regulated as it allows a favorable environment for protein folding, in addition to operate as a major reservoir for fast and specific release of calcium. Altered ER homeostasis impacts protein folding, activating the unfolded protein response (UPR) as a rescue mechanism to restore proteostasis. ER calcium release impacts mitochondrial metabolism and also fine-tunes the threshold to undergo apoptosis under chronic stress. The global coordination between UPR signaling and energetic demands takes place at mitochondrial associated membranes (MAMs), specialized subdomains mediating interorganelle communication. Here we discuss current models explaining the functional relationship between ER homeostasis and various cellular responses to coordinate proteostasis and metabolic maintenance.
内质网 (ER) 钙信号参与了众多协调的细胞过程。内质网钙含量受到严格调节，因为它为蛋白质折叠提供了有利的环境，同时也是快速和特异性释放钙的主要储存库。内质网平衡的改变会影响蛋白质折叠，激活未折叠蛋白反应 (UPR) 作为一种恢复蛋白质稳定性的救援机制。内质网钙释放会影响线粒体代谢，并微调在慢性应激下发生细胞凋亡的阈值。UPR 信号与能量需求之间的全球协调发生在线粒体相关膜 (MAMs) 上，这些特化的亚区介导细胞器间的通讯。在这里，我们讨论了当前的模型，这些模型解释了内质网平衡与各种细胞反应之间的功能关系，以协调蛋白质稳定性和代谢维持。
