ZHANG Yu-Xin, ZHOU Xiao-Jie, YU Hao-Ran, DONG Wan-Yu, YANG Yong-Chun, WANG Xiao-Du, ZHOU Ying-Shan*, SONG Hou-Hui*
College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University / Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province / Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology / Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management / China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou 311300, China
Abstract The endoplasmic reticulum (ER) is a well-orchestrated organelle for protein folding and highly sensitive to changes of cellular homeostasis. Alterations in the protein-folding environment cause accumulation of unfolded/misfolded proteins in the ER which affect a variety of cellular signal transduction pathways, including calcium and redox homeostasis, inflammation, and apoptosis. Upon ER stress, a series of adaptive mechanisms known as the unfolded protein response (UPR) are activated to adapt to protein-folding alterations and restore homeostasis, and failure to adapt to ER stress leads to apoptosis. Production of reactive oxygen species (ROS) has been linked to ER stress and the UPR. ROS has been shown to be toxic but also function as signaling molecules. It can be produced in the cytosol and several organelles, including the ER and mitochondria. Altered redox homeostasis in the ER is sufficient to cause ER stress, which in turn, can induce the production of ROS in the ER and mitochondria. Unremitting oxidative stress and ER stress will initiate apoptosis. In this review, we summarize the mechanism of ER stress and oxidative stress, the intertwined relationship between them, and the emerging roles of the UPR and oxidative stress in viral infections.
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