Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts
Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts
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DOI：
10.1016/j.freeradbiomed.2012.08.591
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发表时间：
2012-11-01
影响因子：
7.4
通讯作者：
Grune, Tilman
中科院分区：
文献类型：
--
作者：
Hoehn, Annika;Sittig, Anna;Grune, Tilman
在目前的文献中，溶酶体系统被认为参与脂褐素的细胞内形成和积累，脂褐素是一种高度氧化和共价交联的蛋白质聚集体，在衰老期间填充溶酶体体积。相反，我们的实验结果表明，自噬体和溶酶体系统都不是强制性的脂褐质的形成，因为如果自噬或溶酶体活性被抑制，该材料在胞质体积中积累。然而，这种抑制伴随着所形成的蛋白质聚集体的增强的毒性。此外，可以证明，大自噬是负责摄取脂褐质进入溶酶体。(C)2012 Elsevier Inc. All rights reserved.
In the current literature, the lysosomal system is considered to be involved in the intracellular formation and accumulation of lipofuscin, a highly oxidized and covalently cross-linked aggregate of proteins that fills the lysosomal volume during aging. In contrast, our experimental results presented here suggest that both the autophagosomes and the lysosomal system are not mandatory for the formation of lipofuscin, since that material accumulates in the cytosolic volume if autophagy or lysosomal activity is inhibited. However, such an inhibition is accompanied by an enhanced toxicity of the formed protein aggregates. Furthermore, it could be proven that macroautophagy is responsible for the uptake of lipofuscin into the lysosomes. (C) 2012 Elsevier Inc. All rights reserved.