TY - JOUR
T1 - Proteostasis is adaptive
T2 - Balancing chaperone holdases against foldases
AU - De Graff, Adam M.R.
AU - Mosedale, David E.
AU - Sharp, Tilly
AU - Dill, Ken A.
AU - Grainger, David J.
N1 - Publisher Copyright:
© 2020 de Graff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/12/14
Y1 - 2020/12/14
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85097674344
U2 - 10.1371/journal.pcbi.1008460
DO - 10.1371/journal.pcbi.1008460
M3 - Article
C2 - 33315891
AN - SCOPUS:85097674344
SN - 1553-734X
VL - 16
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 12
M1 - e1008460
ER -