自噬机制控制细胞死亡在凋亡和坏死性凋亡之间的转换。
The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis.
作者信息
Goodall Megan L, Fitzwalter Brent E, Zahedi Shadi, Wu Min, Rodriguez Diego, Mulcahy-Levy Jean M, Green Douglas R, Morgan Michael, Cramer Scott D, Thorburn Andrew
机构信息
Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045, USA.
Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA.
出版信息
Dev Cell. 2016 May 23;37(4):337-349. doi: 10.1016/j.devcel.2016.04.018.
Although autophagy controls cell death and survival, underlying mechanisms are poorly understood, and it is unknown whether autophagy affects only 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 TRAIL (TNF-related apoptosis-inducing ligand). 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.
尽管自噬控制细胞死亡和存活，但其潜在机制仍知之甚少，并且自噬是否仅影响细胞是否死亡，还是也控制程序性细胞死亡的其他方面尚不清楚。MAP3K7是一种与前列腺癌无病生存期差相关的肿瘤抑制基因。在此，我们报告小鼠前列腺细胞中Map3k7的缺失使细胞对TRAIL（肿瘤坏死因子相关凋亡诱导配体）诱导的细胞死亡敏感。令人惊讶的是，这种死亡主要通过坏死性凋亡而非凋亡发生，这是由于坏死小体与自噬机制结合组装，由p62/SQSTM1招募RIPK1介导。如果p62依赖的坏死小体向自噬机制的招募被阻断，细胞死亡机制会转变为凋亡。这些数据表明，自噬机制可通过作为支架而非降解货物来控制程序性细胞死亡的机制。
Zotero 插件