Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy
Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy
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DOI：
10.1091/mbc.e07-11-1155
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发表时间：
2008-05-01
影响因子：
3.3
通讯作者：
Cuervo, Ana Maria
中科院分区：
文献类型：
--
作者：
Kaushik, Susmita;Massey, Ashish C.;Cuervo, Ana Maria
三种不同类型的自噬-巨型自噬、微型自噬和伴侣介导的自噬(CMA)导致哺乳动物细胞内溶酶体成分的降解。尽管在不同的细胞类型和组织中已经描述了一定水平的基础自噬和CMA活性，但这两条途径在应激条件下被最大限度地激活。这两条途径的激活通常是连续的，这表明两条与应激相关的自噬途径之间存在一定程度的串扰。在这项工作中，我们分析了阻断巨噬细胞自噬对CMA活性的影响。利用缺乏ATG5的小鼠胚胎成纤维细胞，我们发现即使在基础条件下，阻止巨型自噬也会导致CMA的上调。ATG5是自噬形成所需的一种自噬相关蛋白。有趣的是，在这些大型自噬缺陷细胞中，不同的机制导致了观察到的CMA相关蛋白的变化，以及在基础和应激条件下CMA的随后激活。这项工作支持这两种形式的自噬之间的直接相互作用，并确定了溶酶体隔间的变化，这些变化是两种自噬途径之间沟通的基础。
Three different types of autophagy-macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA) contribute to degradation of intracellular components in lysosomes in mammalian cells. Although some level of basal macroautophagy and CMA activities has been described in different cell types and tissues, these two pathways are maximally activated under stress conditions. Activation of these two pathways is often sequential, suggesting the existence of some level of cross-talk between both stress-related autophagic pathways. In this work, we analyze the consequences of blockage of macroautophagy on CMA activity. Using mouse embryonic fibroblasts deficient in Atg5, an autophagy-related protein required for autophagosome formation, we have found that blockage of macroautophagy leads to up-regulation of CMA, even under basal conditions. Interestingly, different mechanisms contribute to the observed changes in CMA-related proteins and the consequent activation of CMA during basal and stress conditions in these macroautophagy-deficient cells. This work supports a direct cross-talk between these two forms of autophagy, and it identifies changes in the lysosomal compartment that underlie the basis for the communication between both autophagic pathways.