Protein degradation sets the fraction of active ribosomes at vanishing growth

Abstract

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 strong qualitative consequences. We propose a simple framework showing that at slow growth protein degradation is balanced by a fraction of "maintenance" ribosomes. Through a detailed analysis of compiled data, we show how this model is predictive with E. coli data and agrees with S. cerevisiae measurements. Intriguingly, model and data show an increased protein degradation 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.

An optimal growth law for RNA composition and its partial implementation through ribosomal and tRNA gene locations in bacterial genomes

“…The proteome degradation rate in E. coli is typically 0.02-0.04 h -1 [52][53][54], which is much smaller than the maximal growth rate. Accordingly, including protein degradation into the model only affects the predictions at very low growth rates in E. coli (Fig A in S1 File).…”

An Optimal Regulation of Fluxes Dictates Microbial Growth In and Out of Steady-State

“…1(E) based on literature values for key parameters (outlined in Supplemental Table 1). Deviations from the prediction for scenario III are only evident for the ribosomal content at very slow growth ( λ ≤ 0.5 hr -1 ) which are hardly observed in any ecologically relevant conditions and can be attributed to additional biological and experimental factors, including protein degradation [74], ribosome inactivation [39,42], and cultures which have not yet reached steady state, factors we discuss in Appendix 8.…”

Resource allocation to cell envelopes and the scaling of bacterial growth rate

“…Hence, the non-zero intercept in Eq 24a. The same idea was recently proposed in [19], and presents the alternative to the idea that the excess ribosomes at slow growth represent the reserve that allows cells to quickly tune their growth to cycles of feast and famine [20]. A similar explanation holds for intercept in the Eq 24b.…”