Rombouts Jan, Tavella Franco, Vandervelde Alexandra, Phong Connie, Ferrell James E, Yang Qiong, Gelens Lendert
Laboratory of Dynamics in Biological Systems, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat, 49, Leuven, Belgium.
Cell Biology and Biophysics Unit and Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
bioRxiv. 2025 Feb 4:2024.12.24.630245. doi: 10.1101/2024.12.24.630245.
Temperature profoundly impacts organismal physiology and ecological dynamics, particularly affecting ectothermic species and making them especially vulnerable to climate changes. Although complex physiological processes usually involve dozens of enzymes, empirically it is found that the rates of these processes often obey the Arrhenius equation, which was originally proposed for individual chemical reactions. Here we have examined the temperature scaling of the early embryonic cell cycle, with the goal of understanding why the Arrhenius equation approximately holds and why it breaks down at temperature extremes. Using experimental data from , , and , plus published data from , and , we find that the apparent activation energies ( values) for the early embryonic cell cycle for diverse ectotherms are all similar, 75 ± 7 kJ/mol (mean ± std.dev., n = 6), which corresponds to a value at 20°C of 2.8 ± 0.2 (mean ± std.dev., n = 6). Using computational models, we find that the approximate Arrhenius scaling and the deviations from it at high and low temperatures can be accounted for by biphasic temperature scaling in critical individual components of the cell cycle oscillator circuit, by imbalances in the values for different partially rate-determining enzymes, or by a combination of both. Experimental studies of cycling extracts indicate that both of these mechanisms contribute to the general scaling of temperature, and studies of individual cell cycle regulators confirm that there is in fact a substantial imbalance in their values. These findings provide mechanistic insights into the dynamic interplay between temperature and complex biochemical processes, and into why biological systems fail at extreme temperatures.
温度对生物体的生理机能和生态动态有着深远影响,尤其会影响变温动物,使它们特别容易受到气候变化的影响。尽管复杂的生理过程通常涉及数十种酶,但从经验上发现,这些过程的速率往往遵循阿仑尼乌斯方程,该方程最初是为单个化学反应提出的。在这里,我们研究了早期胚胎细胞周期的温度标度,目的是了解为什么阿仑尼乌斯方程大致成立,以及为什么它在极端温度下会失效。利用来自[具体实验1]、[具体实验2]和[具体实验3]的实验数据,以及来自[已发表实验1]、[已发表实验2]和[已发表实验3]的已发表数据,我们发现,不同变温动物早期胚胎细胞周期的表观活化能(Ea值)都相似,为75±7kJ/mol(平均值±标准差,n = 6),这对应于20°C时的Ea值为2.8±0.2(平均值±标准差,n = 6)。通过计算模型,我们发现,细胞周期振荡器电路关键单个组件中的双相温度标度、不同部分速率决定酶的Ea值不平衡或两者的结合,可以解释近似的阿仑尼乌斯标度及其在高温和低温下的偏差。对循环提取物的实验研究表明,这两种机制都有助于温度的总体标度,对单个细胞周期调节因子的研究证实,它们的Ea值实际上存在很大不平衡。这些发现为温度与复杂生化过程之间的动态相互作用,以及生物系统在极端温度下为何失效提供了机制上的见解。