Proteostasis is adaptive: Balancing chaperone holdases against foldases.

de Graff, Adam Mr; Mosedale, David E; Sharp, Tilly; Dill, Ken A; Grainger, David J · PLoS Comput Biol · 2020

basic_science · Level V

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Abstract

Because a cell must adapt to different stresses and growth rates, its proteostasis system must too. How do cells detect and adjust proteome folding to different conditions? Here, we explore a biophysical cost-benefit principle, namely that the cell should keep its proteome as folded as possible at the minimum possible energy cost. This can be achieved by differential expression of chaperones-balancing foldases (which accelerate folding) against holdases (which act as parking spots). The model captures changes in the foldase-holdase ratio observed both within organisms during aging and across organisms of varying metabolic rates. This work describes a simple biophysical mechanism by which cellular proteostasis adapts to meet the needs of a changing growth environment.

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