Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 East Clark St, Vermillion, SD 57069, USA.
Circ Res. 2013 Jan 18;112(2):367-81. doi: 10.1161/CIRCRESAHA.112.268706.
Protein quality control functions to minimize the level and toxicity of misfolded proteins in the cell. Protein quality control is performed by intricate collaboration among chaperones and target protein degradation. The latter is performed 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 (eg, mitochondria) and targeting them for degradation by the lysosome. Inadequate protein quality control is observed in a large subset of failing human hearts with a variety of causes, and its pathogenic role has been experimentally demonstrated. Multiple posttranslational modifications can occur to substrate proteins and protein quality control machineries, promoting or hindering the removal of the misfolded proteins. This article highlights recent advances in posttranslational modification-mediated regulation of intracellular quality control mechanisms and its known involvement in cardiac pathology.
蛋白质质量控制功能可最大限度地减少细胞内错误折叠蛋白质的水平和毒性。蛋白质质量控制是通过伴侣蛋白和靶蛋白降解之间的复杂协作来完成的。后者主要由泛素-蛋白酶体系统和自噬来完成。终末错误折叠的蛋白质如果不能及时清除，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地隔离有缺陷的细胞器（例如线粒体）并将其靶向溶酶体进行降解，从而在细胞内质量控制中发挥作用。在多种原因导致的大量衰竭的人类心脏中，观察到蛋白质质量控制不足，其致病作用已在实验中得到证实。底物蛋白和蛋白质质量控制机制可以发生多种翻译后修饰，促进或阻碍错误折叠蛋白质的清除。本文重点介绍了翻译后修饰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作用。
