The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis.
The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis.
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DOI：
10.1016/j.devcel.2016.04.018
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发表时间：
2016-05-23
影响因子：
11.8
通讯作者：
Thorburn A
中科院分区：
文献类型：
--
作者：
Goodall ML;Fitzwalter BE;Zahedi S;Wu M;Rodriguez D;Mulcahy-Levy JM;Green DR;Morgan M;Cramer SD;Thorburn A
虽然自噬控制细胞死亡和存活，但其潜在机制尚不清楚，也不知道自噬是否仅影响细胞死亡或控制程序性细胞死亡的其他方面。MAP 3 K7是一种与前列腺癌无病生存率低相关的肿瘤抑制基因。在这里，我们报告说，Map 3 k7在小鼠前列腺细胞的缺失敏化细胞死亡的肿瘤坏死因子相关的凋亡诱导配体（TRAIL）。令人惊讶的是，这种死亡主要通过坏死性凋亡而不是凋亡发生，这是由于与自噬机制相关的坏死体的组装，由P62/SQSTM 1募集RIPK 1介导。如果坏死体向自噬机制的p62依赖性募集被阻断，则细胞死亡的机制切换为凋亡。这些数据表明，自噬机制可以通过充当支架而不是通过降解货物来控制程序性细胞死亡的机制。
Although autophagy controls cell death and survival, underlying mechanisms are poorly understood and it is unknown if autophagy just affects whether or not cells die or also controls other aspects of programmed cell death. MAP3K7 is a tumor suppressor gene associated with poor disease-free survival in prostate cancer. Here we report that Map3k7 deletion in mouse prostate cells sensitizes to cell death by TNF-related apoptosis inducing ligand (TRAIL). Surprisingly, this death occurs primarily through necroptosis, not apoptosis, due to assembly of the necrosome in association with the autophagy machinery, mediated by p62/SQSTM1 recruitment of RIPK1. The mechanism of cell death switches to apoptosis if p62-dependent recruitment of the necrosome to the autophagy machinery is blocked. These data show that the autophagy machinery can control the mechanism of programmed cell death by serving as a scaffold rather than by degrading cargo.