Autophagy is an important cell activity which is the process of formation of autophagosomes, docking with lysosomes and degradation. The intrinsic pathway of apoptosis involves mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release followed by caspase activation. Many molecules, e.g., Ca 2+ and mTOR, and different stresses such as endoplasmic reticulum (ER) stress and nutritional stress take part in these two processes. However, the mechanism of how they work together so as to determine cell fate decisions remains to be clarified. Here, we present a computational model for cell fate decisions based on intertwined dynamics with autophagy and apoptosis involving Ca 2+ , mTOR, and both ER stress and nutritional stress. In agreement with experimental observations, the model predicts that both Ca 2+ and the stresses play critical roles in regulating the choice between autophagy and apoptosis in a combinatorial way. The model presented here might be a good candidate for providing the qualitative mechanism of cell fate decisions mediated by Ca 2+ , mTOR, and two kinds of stress.

中文翻译：

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哺乳动物细胞自噬和细胞凋亡的串扰介导的命运决定

自噬是一种重要的细胞活动，是自噬体形成、与溶酶体对接和降解的过程。细胞凋亡的内在途径涉及线粒体外膜透化 (MOMP) 和细胞色素 c 释放，然后是半胱天冬酶激活。许多分子，例如Ca 2+ 和mTOR，以及不同的应激如内质网（ER）应激和营养应激参与这两个过程。然而，它们如何协同工作以决定细胞命运的机制仍有待澄清。在这里，我们提出了一个细胞命运决定的计算模型，该模型基于与自噬和细胞凋亡的交织动力学，涉及 Ca 2+ 、mTOR 以及内质网应激和营养应激。与实验观察一致，该模型预测，Ca 2+ 和应激在以组合方式调节自噬和细胞凋亡之间的选择中起着关键作用。这里提出的模型可能是提供由 Ca 2+ 、mTOR 和两种压力介导的细胞命运决定定性机制的一个很好的候选者。