Liver function and dysfunction - a unique window into the physiological reach of ER stress and the unfolded protein response.
Liver function and dysfunction - a unique window into the physiological reach of ER stress and the unfolded protein response.
复制标题
DOI：
10.1111/febs.14389
复制
发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Rutkowski DT
中科院分区：
文献类型：
--
作者：
Rutkowski DT
未折叠蛋白反应(UPR)促进内质网(ER)蛋白折叠，以缓解压力。然而，越来越清楚的是，UPR对蛋白质折叠的调控远远超出了那些直接参与蛋白质折叠的过程，在某些情况下，调控机制超出了规范的UPR信号范围。这些通路从一种细胞类型到另一种细胞类型是高度特异的，这意味着内质网应激信号以独特的方式影响每个组织。或许，这一点在肝脏中最为明显，它不仅是一个高度分泌的组织，而且是外周新陈代谢的关键调节器，在受损时是一个独特的增殖器官。肝脏提供了一个强大的模型系统，用于探索UPR如何以及为什么将其覆盖范围扩展到内质网之外的生理过程，以及内质网应激如何导致涉及肝功能障碍的许多系统性疾病。这篇综述将重点介绍对肝脏内质网应激的研究如何扩大了UPR的观点，使其成为细胞内稳态的关键守护者，而不仅仅是ER蛋白折叠的狭窄领域。在应激过程中，未折叠蛋白反应(UPR)恢复内质网稳态。在肝脏中，UPR受到新陈代谢和肝脏损伤的调节，并反过来促进代谢和肝脏损伤。这篇综述强调了这些联系，以及它们告诉我们关于肝脏的生理学和病理生理学以及UPR的细胞生物学的信息。
The unfolded protein response (UPR) improves endoplasmic reticulum (ER) protein folding in order to alleviate stress. Yet it is becoming increasingly clear that the UPR regulates processes well beyond those directly involved in protein folding, in some cases by mechanisms that fall outside the realm of canonical UPR signaling. These pathways are highly specific from one cell type to another, implying that ER stress signaling affects each tissue in a unique way. Perhaps nowhere is this more evident than in the liver, which—beyond being a highly secretory tissue—is a key regulator of peripheral metabolism and a uniquely proliferative organ upon damage. The liver provides a powerful model system for exploring how and why the UPR extends its reach into physiological processes that occur outside the ER, and how ER stress contributes to the many systemic diseases that involve liver dysfunction. This review will highlight the ways in which the study of ER stress in the liver has expanded the view of the UPR to a response that is a key guardian of cellular homeostasis outside of just the narrow realm of ER protein folding. The unfolded protein response (UPR) restores ER homeostasis during stress. In the liver, the UPR is regulated by—and in turn contributes to—both metabolism and liver damage. This review highlights these connections and what they tell us about both the physiology and pathophysiology of the liver and the cell biology of the UPR.
登录
查看更多内容
影响因子：
3.7
作者：
Badr CE;Hewett JW;Breakefield XO;Tannous BA
通讯作者：
Tannous BA
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1074/jbc.m111.228817
发表时间：
2011-10-21
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Birkenfeld AL;Lee HY;Majumdar S;Jurczak MJ;Camporez JP;Jornayvaz FR;Frederick DW;Guigni B;Kahn M;Zhang D;Weismann D;Arafat AM;Pfeiffer AF;Lieske S;Oyadomari S;Ron D;Samuel VT;Shulman GI
通讯作者：
Shulman GI
影响因子：
25.7
作者：
Fausto, N
通讯作者：
Fausto, N
肝脏 ATF6 通过过氧化物酶体增殖物激活受体 α 增加脂肪酸氧化，减轻小鼠肝脏脂肪变性
影响因子：
7.7
作者：
Chen, Xuqing;Zhang, Feifei;Li, Yu
通讯作者：
Li, Yu