Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001, China.
Adv Exp Med Biol. 2019;1206:167-177. doi: 10.1007/978-981-15-0602-4_8.
In 1945, K. R. Porter et al. observed mouse embryonic fibroblasts (MEFs) and found that the cytoplasmic part of the cell had an unreported reticular structure, so it was named endoplasmic reticulum (ER). The major functions of the endoplasmic reticulum are: synthesis of intracellular proteins and the modification and processing of proteins. It is an important organelle in eukaryotic cells. It is a three-dimensional network structure in which complex and closed intracellular tubular intimal systems are intertwined. When cells are subjected to various strong stimulating factors such as nutrient deficiencies, Ca metabolic imbalance, toxin stimulation, and sustained oxidative stress stimulation, the cell homeostasis will be broken. In order to survive, a series of cell self-protection event will be initiated including the endoplasmic reticulum stress (ERS). The UPR can further promote the expression of the proteins which can help the misfolded and unfolded proteins restore to its normal structure through the activation of PERK, IRE1, and ATF6. However, the co-working of UPR and the ubiquitin-proteasome system still cannot make the endoplasmic reticulum restoring to its normal state, when the stimuli persist or are too strong. The damaged endoplasmic reticulum can be partially engulfed by the autophagic vesicles for degradation when the ERS persists. The degraded endoplasmic reticulum fragments can be reassembled into a new endoplasmic reticulum to restore the normal state of it. Hence, it seems that the autophagy has become the last mean to restore the homeostasis of endoplasmic reticulum.
1945 年，K.R.波特等人观察到小鼠胚胎成纤维细胞（MEFs），发现细胞质部分有一种未报告的网状结构，因此将其命名为内质网（ER）。内质网的主要功能是：合成细胞内蛋白质和蛋白质的修饰和加工。它是真核细胞中的一种重要细胞器。它是一种三维网络结构，其中复杂而封闭的细胞内管状内膜系统相互交织。当细胞受到各种强烈刺激因素的影响，如营养缺乏、钙代谢失衡、毒素刺激和持续氧化应激刺激时，细胞内稳态就会被打破。为了生存，细胞会启动一系列自我保护事件，包括内质网应激（ERS）。UPR 可以通过激活 PERK、IRE1 和 ATF6，进一步促进有助于错误折叠和未折叠蛋白质恢复正常结构的蛋白质的表达。然而，当刺激持续或过强时，UPR 和泛素蛋白酶体系统的共同作用仍然不能使内质网恢复正常状态。当 ERS 持续存在时，受损的内质网可以被自噬小泡部分吞噬进行降解。降解的内质网片段可以重新组装成新的内质网，恢复其正常状态。因此，自噬似乎已成为恢复内质网内稳态的最后手段。
