IFOM Foundation, FIRC Institute for Molecular Oncology, Milan, Italy.
Quantitative Life Sciences section, The Abdus Salam International Centre for Theoretical Physics (ICTP), Trieste, Italy.
PLoS Comput Biol. 2022 May 2;18(5):e1010059. doi: 10.1371/journal.pcbi.1010059. eCollection 2022 May.
Growing cells adopt common basic strategies to achieve optimal resource allocation under limited resource availability. Our current understanding of such "growth laws" neglects degradation, assuming that it occurs slowly compared to the cell cycle duration. Here we argue that this assumption cannot hold at slow growth, leading to important consequences. We propose a simple framework showing that at slow growth protein degradation is balanced by a fraction of "maintenance" ribosomes. Consequently, active ribosomes do not drop to zero at vanishing growth, but as growth rate diminishes, an increasing fraction of active ribosomes performs maintenance. Through a detailed analysis of compiled data, we show that the predictions of this model agree with data from E. coli and S. cerevisiae. Intriguingly, we also find that protein degradation increases at slow growth, which we interpret as a consequence of active waste management and/or recycling. Our results highlight protein turnover as an underrated factor for our understanding of growth laws across kingdoms.
细胞在资源有限的情况下会采取共同的基本策略来实现最佳资源分配。我们目前对这些“生长规律”的理解忽略了降解,假设降解与细胞周期持续时间相比缓慢发生。在这里,我们认为这种假设在生长缓慢时不能成立,这会导致重要的后果。我们提出了一个简单的框架,表明在生长缓慢时,蛋白质降解与一部分“维持”核糖体平衡。因此,在生长停止时,活性核糖体不会降为零,而是随着生长速率的降低,越来越多的活性核糖体用于维持。通过对编译数据的详细分析,我们表明该模型的预测与大肠杆菌和酿酒酵母的数据相符。有趣的是,我们还发现蛋白质降解在生长缓慢时增加,我们将其解释为活性废物管理和/或回收的结果。我们的研究结果强调了蛋白质周转是理解不同生物界生长规律的一个被低估的因素。