Life in the balance - a mechanistic view of the crosstalk between autophagy and apoptosis
Life in the balance - a mechanistic view of the crosstalk between autophagy and apoptosis
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DOI：
10.1242/jcs.115865
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发表时间：
2012-11-15
影响因子：
4
通讯作者：
Kimchi, Adi
中科院分区：
文献类型：
--
作者：
Rubinstein, Assaf D.;Kimchi, Adi
细胞应激在细胞中触发了一个迷人的决策过程;它们可以尝试生存，直到通过激活细胞保护途径（如自噬）解决应激，或者可以通过凋亡自杀，以防止对周围健康细胞的进一步损害。虽然自噬和凋亡构成了不同的细胞过程，往往相反的结果，它们的信号转导途径是广泛的相互联系，通过各种机制的串扰。自噬-凋亡串扰的生理相关性还没有很好地理解，但据推测，它有助于对给定应激信号的受控和良好平衡的细胞反应。在这篇评论中，我们探讨了自噬和凋亡相互调节的各种机制，并根据机械特征定义了串扰的一般范式。一个范例涉及特异性凋亡和自噬蛋白对之间的物理和功能相互作用。在第二种机制范例中，细胞凋亡或自噬过程（与单个蛋白质相反）分别通过诱导的半胱天冬酶和自体溶酶体活性相互调节。在自噬特有的第三种模式中，半胱天冬酶在自噬体膜上被募集和激活。这些机制的范例是可辨别的实验，因此可以作为一个实际的指导实验数据的解释。
Cellular stress triggers a fascinating decision-making process in cells; they can either attempt to survive until the stress is resolved through the activation of cytoprotective pathways, such as autophagy, or can commit suicide by apoptosis in order to prevent further damage to surrounding healthy cells. Although autophagy and apoptosis constitute distinct cellular processes with often opposing outcomes, their signalling pathways are extensively interconnected through various mechanisms of crosstalk. The physiological relevance of the autophagy-apoptosis crosstalk is not well understood, but it is presumed to facilitate a controlled and well-balanced cellular response to a given stress signal. In this Commentary, we explore the various mechanisms by which autophagy and apoptosis regulate each other, and define general paradigms of crosstalk on the basis of mechanistic features. One paradigm relates to physical and functional interactions between pairs of specific apoptotic and autophagic proteins. In a second mechanistic paradigm, the apoptosis or autophagy processes (as opposed to individual proteins) regulate each other through induced caspase and autolysosomal activity, respectively. In a third paradigm unique to autophagy, caspases are recruited and activated on autophagosomal membranes. These mechanistic paradigms are discernible experimentally, and can therefore be used as a practical guide for the interpretation of experimental data.