Protein Misfolding and Cellular Stress: An Overview
Protein Misfolding and Cellular Stress: An Overview
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DOI：
10.1007/978-1-60761-756-3_1
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Bross, Peter
中科院分区：
文献类型：
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作者：
Gregersen, Niels;Bross, Peter
细胞生存和死亡是复杂的问题。太多的存活可能会导致癌症，太多的细胞死亡可能会导致组织退化。在本章中，我们首先将重点放在促进蛋白质正确折叠和维持功能的细胞生存机制上。这些机制包括蛋白质质量控制(PQC)系统，包括胞浆、内质网(ER)和线粒体中的分子伴侣和细胞内蛋白水解酶。除了PQC系统外，错误折叠的蛋白质引发的机制，称为未折叠蛋白反应(UPR)，包括抗氧化系统的诱导/激活，也存在于细胞的三个隔室。其次，我们将讨论错误折叠的蛋白质导致以活性氧物种(ROS)和活性氮物种(RNS)的形式产生氧化应激的机制。这些物种主要由线粒体呼吸链产生的超氧化物(O-2(-))和线粒体氮氧化物合成酶(MtNOS)产生的氮氧化物(NO)产生。第三，将讨论氧化应激的影响，包括线粒体动力学，即分裂和融合，以及相关的细胞清理系统消除功能障碍的线粒体，即有丝分裂或有丝分裂，以及与氧化修饰蛋白质的产生和细胞效应有关的影响，从而结束蛋白质错误折叠和氧化应激的恶性循环。
Cell survival and death arc complex matters. Too much survival may lead to cancer and too much cell death may result in tissue degeneration. In this chapter, we will first of all focus on the cellular survival mechanisms that promote correct folding and maintenance of protein function. These mechanisms include protein quality control (PQC) systems comprising molecular chaperones and intracellular proteases in the cytosol, endoplasmatic reticulum (ER) and in the mitochondria. In addition to the PQC systems, mechanisms elicited by misfolded proteins, known as unfolded protein responses (UPRs), including induction/activation of antioxidant systems arc also present in the three compartments of the cell. Second, we will discuss the mechanisms by which misfolded proteins lead to the generation of oxidative stress in the form of reactive oxygen species (ROS) and reactive nitrogen species (RNS). These species are produced mainly from superoxide (O-2(-)) generated in the mitochondrial respiratory chain and from nitrogen oxide (NO) produced by the mitochondrial nitrogen oxide synthetase (mtNOS). Third, the effects of oxidative stress will be discussed, both with respect to mitochondrial dynamics, i.e., fission and fusion, and the related elimination of dysfunctional mitochondria by cellular cleaning systems, i.e., mitophagy or mitoptosis, and related to the generation and cellular effects of oxidatively modified proteins, which closes a vicious cycle of protein misfolding and oxidative stress.