FEBS J. 2014 Feb;281(3):825-41. doi: 10.1111/febs.12649.
In this article, we aim to find an explanation for the surprisingly thin line, with regard to temperature, between cell growth, growth arrest and ultimately loss of cell viability. To this end, we used an integrative approach including both experimental and modelling work. We measured the short- and long-term effects of increases in growth temperature from 28 °C to 37, 39, 41, 42 or 43 °C on the central metabolism of Saccharomyces cerevisiae. Based on the experimental data, we developed a kinetic mathematical model that describes the metabolic and energetic changes in growing bakers' yeast when exposed to a specific temperature upshift. The model includes the temperature dependence of core energy-conserving pathways, trehalose synthesis, protein synthesis and proteolysis. Because our model focuses on protein synthesis and degradation, the net result of which is important in determining the cell's capacity to grow, the model includes growth, i.e. glucose is consumed and biomass and adenosine nucleotide cofactors are produced. The model reproduces both the observed initial metabolic response and the subsequent relaxation into a new steady-state, compatible with the new ambient temperature. In addition, it shows that the energy consumption for proteome reprofiling may be a major determinant of heat-induced growth arrest and subsequent recovery or cell death.
本文旨在探讨细胞生长、生长停滞，乃至最终丧失活力之间的界限为何如此之窄，温度在其中起着关键作用。为此，我们采用了综合的方法，包括实验和建模工作。我们测量了从 28°C 升高到 37、39、41、42 或 43°C 对酿酒酵母中心代谢的短期和长期影响。基于实验数据，我们开发了一个描述面包酵母在受到特定温度升高时代谢和能量变化的动力学数学模型。该模型包括核心能量守恒途径、海藻糖合成、蛋白质合成和蛋白水解的温度依赖性。由于我们的模型侧重于蛋白质的合成和降解，而这对决定细胞生长能力至关重要，因此模型包括生长，即葡萄糖被消耗，生物质和腺苷核苷酸辅因子被产生。该模型重现了观察到的初始代谢反应以及随后适应新环境温度的松弛过程。此外，它表明，蛋白质组重编程所需的能量消耗可能是热诱导生长停滞以及随后的恢复或细胞死亡的主要决定因素。
