Cellular proteostasis: degradation of misfolded proteins by lysosomes.
Cellular proteostasis: degradation of misfolded proteins by lysosomes.
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DOI：
10.1042/ebc20160005
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发表时间：
2016-10-15
影响因子：
6.4
通讯作者：
Hewitt EW
中科院分区：
文献类型：
--
作者：
Jackson MP;Hewitt EW
蛋白质稳定是指组成蛋白质组的每种蛋白质的细胞浓度、折叠、相互作用和定位的调节。蛋白质稳态的一个基本要素是通过蛋白质降解的细胞途径处置错误折叠的蛋白质。溶酶体是错误折叠蛋白降解的重要场所，错误折叠蛋白通过大自噬、分子伴侣介导的自噬和内吞作用途径转运至溶酶体。相反，淀粉样蛋白疾病代表蛋白质稳态的失败，其中蛋白质错误折叠，形成不能被细胞有效降解的淀粉样蛋白沉积物。淀粉样蛋白可能通过破坏自噬和溶酶体蛋白水解而加剧这种失败。然而，靶向调节自噬和溶酶体生物发生的途径可能会提出可以将细胞从淀粉样蛋白的有害作用中拯救出来的方法。
Proteostasis refers to the regulation of the cellular concentration, folding, interactions and localization of each of the proteins that comprise the proteome. One essential element of proteostasis is the disposal of misfolded proteins by the cellular pathways of protein degradation. Lysosomes are an important site for the degradation of misfolded proteins, which are trafficked to this organelle by the pathways of macroautophagy, chaperone-mediated autophagy and endocytosis. Conversely, amyloid diseases represent a failure in proteostasis, in which proteins misfold, forming amyloid deposits that are not degraded effectively by cells. Amyloid may then exacerbate this failure by disrupting autophagy and lysosomal proteolysis. However, targeting the pathways that regulate autophagy and the biogenesis of lysosomes may present approaches that can rescue cells from the deleterious effects of amyloidogenic proteins.