Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.
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DOI：
10.1371/journal.pbio.0040423
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发表时间：
2006-11
期刊：
影响因子：
9.8
通讯作者：
Walter P
中科院分区：
文献类型：
--
作者：
Bernales S;McDonald KL;Walter P
内质网 (ER) 的蛋白质折叠能力受未折叠蛋白质反应 (UPR) 的调节。 UPR 感知内质网腔中未折叠的蛋白质，并将该信息传输到细胞核，在细胞核中驱动转录程序，以重新建立体内平衡。使用薄片电子显微镜，我们发现酵母细胞在 UPR 诱导条件下将其内质网体积扩大至少 5 倍。令人惊讶的是，我们发现内质网增殖伴随着自噬体样结构的形成，这些结构密集且选择性地填充了源自 UPR 扩增的内质网的膜堆叠。与 pexophagy 和 mitophagy（选择性地隔离和降解过氧化物酶体和线粒体的自噬过程）类似，所描述的 ER 特异性自噬过程利用了几种自噬基因：它们由 UPR 诱导，对于遭受严重 ER 应激的细胞的生存至关重要。有趣的是，细胞存活不需要液泡蛋白酶，这表明内质网隔离到自噬体样结构中，而不是它们的降解，是重要的一步。即使面对不断积累的未折叠蛋白，选择性 ER 隔离也可以帮助细胞维持新的稳态 ER 丰度水平。作者描述了由未折叠蛋白反应 (UPR) 诱导的 ER 特异性自噬过程，该过程将 ER 隔离到自噬体样体中。当未折叠的蛋白质在细胞内积累时，这个过程可能涉及重建体内平衡。
The protein folding capacity of the endoplasmic reticulum (ER) is regulated by the unfolded protein response (UPR). The UPR senses unfolded proteins in the ER lumen and transmits that information to the cell nucleus, where it drives a transcriptional program that is tailored to re-establish homeostasis. Using thin section electron microscopy, we found that yeast cells expand their ER volume at least 5-fold under UPR-inducing conditions. Surprisingly, we discovered that ER proliferation is accompanied by the formation of autophagosome-like structures that are densely and selectively packed with membrane stacks derived from the UPR-expanded ER. In analogy to pexophagy and mitophagy, which are autophagic processes that selectively sequester and degrade peroxisomes and mitochondria, the ER-specific autophagic process described utilizes several autophagy genes: they are induced by the UPR and are essential for the survival of cells subjected to severe ER stress. Intriguingly, cell survival does not require vacuolar proteases, indicating that ER sequestration into autophagosome-like structures, rather than their degradation, is the important step. Selective ER sequestration may help cells to maintain a new steady-state level of ER abundance even in the face of continuously accumulating unfolded proteins. The authors describe an ER-specific autophagic process induced by the unfolded protein response (UPR), which sequesters ER into autophagosome-like bodies. This process may be involved in re-establishing homeostasis when unfolded proteins accumulate inside cells.
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影响因子：
7.8
作者：
Baba, M;Osumi, M;Scott, SV;Klionsky, DJ;Ohsumi, Y
通讯作者：
Ohsumi, Y
酵母突变体在细胞质中的分离和表征与液泡蛋白靶向途径的分离。
影响因子：
7.8
作者：
HARDING, TM;MORANO, KA;SCOTT, SV;KLIONSKY, DJ
通讯作者：
KLIONSKY, DJ
影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
3.2
作者：
FELDMAN, D;SWARM, RL;BECKER, J
通讯作者：
BECKER, J
影响因子：
2.5
作者：
Bellu, AR;Kiel, JAKW
通讯作者：
Kiel, JAKW