Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events.
Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events.
复制标题
DOI：
10.1038/s41419-021-03599-7
复制
发表时间：
2021-03-23
影响因子：
9
通讯作者：
Korcsmáros T
中科院分区：
文献类型：
--
作者：
Kapuy O;Holczer M;Márton M;Korcsmáros T
尽管自噬是一种程序性细胞死亡，但它对于细胞在各种应激事件的可耐受水平下的生存也至关重要。为了使细胞对细胞应激诱导的外部和/或内部刺激做出充分反应，必须以高度调控的方式控制自噬。通过使用系统生物学技术，我们探讨了自噬诱导的动力学特征。我们提出自噬诱导的类似开关特性是通过控制网络实现的，该控制网络包含四个组件的基本反馈回路，分别称为自噬诱导器、自噬控制器、mTORC1 和自噬执行器。我们展示了自噬诱导剂如何能够以细胞应激特异性方式开启自噬。自噬控制器充当分子开关，不仅促进自噬，还通过下调自噬诱导剂来阻止该过程的永久过度激活。在这个理论分析中，我们详细探讨了所有四个提出的控制元素的属性及其联系。在这里，我们还证明了该控制网络的动力学特征在各种应激过程（例如饥饿、内质网应激和氧化应激）中可以被认为是准确的，即使确切的成分可能不同。在细胞应激期间，由此产生的控制网络的稳健响应至关重要。
Although autophagy is a type of programmed cell death, it is also essential for cell survival upon tolerable level of various stress events. For the cell to respond adequately to an external and/or internal stimulus induced by cellular stress, autophagy must be controlled in a highly regulated manner. By using systems biology techniques, here we explore the dynamical features of autophagy induction. We propose that the switch-like characteristic of autophagy induction is achieved by a control network, containing essential feedback loops of four components, so-called autophagy inducer, autophagy controller, mTORC1 and autophagy executor, respectively. We show how an autophagy inducer is capable to turn on autophagy in a cellular stress-specific way. The autophagy controller acts as a molecular switch and not only promotes autophagy but also blocks the permanent hyperactivation of the process via downregulating the autophagy inducer. In this theoretical analysis, we explore in detail the properties of all four proposed controlling elements and their connections. Here we also prove that the kinetic features of this control network can be considered accurate in various stress processes (such as starvation, endoplasmic reticulum stress and oxidative stress), even if the exact components may be different. The robust response of the resulting control network is essential during cellular stress.
登录
查看更多内容
AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
16
作者：
Harding, HP;Zhang, YH;Ron, D
通讯作者：
Ron, D
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
4.8
作者：
Jain, Ashish;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
64.5
作者：
Green DR;Levine B
通讯作者：
Levine B