Kopito R R, Sitia R
Department of Biological Sciences, Stanford University, CA 94305-5020, USA.
EMBO Rep. 2000 Sep;1(3):225-31. doi: 10.1093/embo-reports/kvd052.
All cells are equipped with a proteolytic apparatus that eliminates damaged, misfolded and incorrectly assembled proteins. The principal engine of cytoplasmic proteolysis, the 26S proteasome, requires that substrates be unfolded to gain access to the active site; consequently, it is relatively ineffective at degrading aggregated proteins. Cellular indigestion occurs when the production of aggregation-prone proteins exceeds the cell's (or organelle's) capacity to eliminate them. Cellular pathways that resolve this indigestion exist, but appear to have limited capacities. Russell bodies and aggresomes are manifestations of cellular indigestion in the endoplasmic reticulum and cytoplasmic compartments, respectively, and are often associated with disease.
所有细胞都配备有一个蛋白水解装置，用于清除受损、错误折叠和组装错误的蛋白质。细胞质蛋白水解的主要引擎——26S蛋白酶体，要求底物展开才能进入活性位点；因此，它在降解聚集蛋白方面相对无效。当易于聚集的蛋白质的产生超过细胞（或细胞器）清除它们的能力时，就会发生细胞消化不良。解决这种消化不良的细胞途径是存在的，但似乎能力有限。拉塞尔小体和聚集体分别是内质网和细胞质区室中细胞消化不良的表现，并且常常与疾病相关。
