Autophagy as a cell-repair mechanism: Activation of chaperone-mediated autophagy during oxidative stress
Autophagy as a cell-repair mechanism: Activation of chaperone-mediated autophagy during oxidative stress
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DOI：
10.1016/j.mam.2006.08.007
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发表时间：
2006-10-01
影响因子：
10.6
通讯作者：
Cuervo, A. M.
中科院分区：
文献类型：
--
作者：
Kaushik, S.;Cuervo, A. M.
当评估细胞处理氧化应激的能力时，氧化蛋白的适当去除是成功的重要决定因素。泛素/蛋白酶体系统被认为是去除氧化蛋白的主要机制，因为它可以区分正常和改变的蛋白质，并选择性地靶向后者进行降解。另一个主要的细胞内蛋白水解系统溶酶体在去除氧化蛋白中的可能作用经常被拒绝，主要是基于该系统缺乏选择性。尽管溶酶体中细胞内组分的大部分降解（自噬）通过完整胞质区域的“大量”隔离发生，但是通过所谓的伴侣介导的自噬（CMA）将蛋白质选择性靶向溶酶体以用于其降解也是可能的。在这项工作中，我们回顾了最近的证据支持CMA参与清除氧化蛋白的细胞反应氧化应激的最前沿。CMA活动的损害，在老化过程中观察到的后果，并在一些与年龄有关的疾病，也进行了讨论。(c)2006爱思唯尔有限公司保留所有权利。
Proper removal of oxidized proteins is an important determinant of success when evaluating the ability of cells to handle oxidative stress. The ubiquitin/proteasome system has been considered the main responsible mechanism for the removal of oxidized proteins, as it can discriminate between normal and altered proteins, and selectively target the latter ones for degradation. A possible role for lysosomes, the other major intracellular proteolytic system, in the removal of oxidized proteins has been often refused, mostly on the basis of the lack of selectivity of this system. Although most of the degradation of intracellular components in lysosomes (autophagy) takes place through "in bulk" sequestration of complete cytosolic regions, selective targeting of proteins to lysosomes for their degradation is also possible via what is known as chaperone-mediated autophagy (CMA). In this work, we review recent evidence supporting the participation of CMA in the clearance of oxidized proteins in the forefront of the cellular response to oxidative stress. The consequences of an impairment in CMA activity, observed during aging and in some age-related disorders, are also discussed. (c) 2006 Elsevier Ltd. All rights reserved.