Fonseca Luís L, Sánchez Claudia, Santos Helena, Voit Eberhard O
Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, 2780-156 Oeiras, Portugal.
Mol Biosyst. 2011 Mar;7(3):731-41. doi: 10.1039/c0mb00102c. Epub 2010 Nov 18.
Cells and organisms are regularly exposed to a variety of stresses, and effective responses are a matter of survival. The article describes a multi-scale experimental and dynamical modeling analysis that clearly indicates concerted stress control in different temporal and organizational domains, and a strong synergy between the dynamics of genes, proteins and metabolites. Specifically, we show with in vivo NMR measurements of metabolic profiles that baker's yeast responds to a paradigmatic stress, heat, at three organizational levels and in two time regimes. At the metabolic level, an almost immediate response is mounted. However, this response is a "quick fix" in comparison to a much more effective response that had been pre-organized in earlier periods of heat stress and is an order of magnitude stronger. Equipped with the metabolic profile data, our modeling efforts resulted in a crisp, quantitative separation of response actions at the levels of metabolic control and gene regulation. They also led to predictions of necessary changes in protein levels and clearly demonstrated that formerly observed temperature profiles of key enzyme activities are not sufficient to explain the accumulation of trehalose as an immediate response to sudden heat stress.
细胞和生物体经常会受到各种应激，而有效的应激反应是生存的关键。本文描述了一项多尺度实验和动力学建模分析，该分析清楚地表明了在不同时间和组织层面上的协同应激控制，以及基因、蛋白质和代谢物动力学之间的强大协同作用。具体而言，我们通过对代谢谱的体内核磁共振测量表明，面包酵母在三个组织层面和两个时间阶段对典型应激——热应激做出反应。在代谢水平上，几乎会立即产生反应。然而，与在早期热应激阶段预先组织好的更有效反应相比，这种反应只是一种“权宜之计”，且效力要高出一个数量级。基于代谢谱数据，我们的建模工作在代谢控制和基因调控层面上对反应行为进行了清晰、定量的区分。这些工作还预测了蛋白质水平的必要变化，并清楚地表明，以前观察到的关键酶活性温度谱不足以解释海藻糖作为对突然热应激的即时反应而积累的现象。
