Posttranslational modification and quality control.
Posttranslational modification and quality control.
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DOI：
10.1161/circresaha.112.268706
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发表时间：
2013-01-18
影响因子：
20.1
通讯作者：
Su H
中科院分区：
文献类型：
--
作者：
Wang X;Pattison JS;Su H
蛋白质质量控制 (PQC) 的作用是最大限度地降低细胞中错误折叠蛋白质的水平和毒性。 PQC 是通过分子伴侣和目标蛋白降解之间复杂的协作来执行的。后者主要由泛素-蛋白酶体系统和可能的自噬进行。未及时去除的最终错误折叠蛋白质往往会形成聚集体。它们的清除需要巨自噬。巨自噬还通过选择性分离有缺陷的细胞器（例如线粒体）并靶向它们由溶酶体降解来用于细胞内质量控制。在大量具有多种病因的人类心脏衰竭中观察到 PQC 不足，其致病作用已通过实验得到证实。底物蛋白和/或 PQC 机制可能会发生多种翻译后修饰 (PTM)，从而促进或阻碍错误折叠蛋白的去除。本文重点介绍了 PTM 介导的细胞内质量控制机制调节的最新进展及其在心脏病理学中的已知参与。
Protein quality control (PQC) functions to minimize the level and toxicity of misfolded proteins in the cell. PQC is performed by intricate collaboration among chaperones and target protein degradation. The latter is carried out primarily by the ubiquitin-proteasome system and perhaps autophagy. Terminally misfolded proteins that are not timely removed tend to form aggregates. Their clearance requires macroautophagy. Macroautophagy serves in intracellular quality control also by selectively segregating defective organelles (e.g., mitochondria) and targeting them for degradation by the lysosome. Inadequate PQC is observed in a large subset of failing human hearts with a variety of etiologies and its pathogenic role has been experimentally demonstrated. Multiple post-translational modifications (PTMs) can occur to substrate proteins and/or PQC machineries, promoting or hindering the removal of the misfolded proteins. This article highlights recent advances in PTMs-mediated regulation of intracellular quality control mechanisms and its known involvement in cardiac pathology.