Repair or Degrade: the Thermodynamic Dilemma of Cellular Protein Quality-Control.

Details

Serval ID
serval:BIB_26CBAF0FE2AB
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Repair or Degrade: the Thermodynamic Dilemma of Cellular Protein Quality-Control.
Journal
Frontiers in molecular biosciences
Author(s)
Fauvet B., Rebeaud M.E., Tiwari S., De Los Rios P., Goloubinoff P.
ISSN
2296-889X (Print)
ISSN-L
2296-889X
Publication state
Published
Issued date
2021
Peer-reviewed
Oui
Volume
8
Pages
768888
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: epublish
Abstract
Life is a non-equilibrium phenomenon. Owing to their high free energy content, the macromolecules of life tend to spontaneously react with ambient oxygen and water and turn into more stable inorganic molecules. A similar thermodynamic picture applies to the complex shapes of proteins: While a polypeptide is emerging unfolded from the ribosome, it may spontaneously acquire secondary structures and collapse into its functional native conformation. The spontaneity of this process is evidence that the free energy of the unstructured state is higher than that of the structured native state. Yet, under stress or because of mutations, complex polypeptides may fail to reach their native conformation and form instead thermodynamically stable aggregates devoid of biological activity. Cells have evolved molecular chaperones to actively counteract the misfolding of stress-labile proteins dictated by equilibrium thermodynamics. HSP60, HSP70 and HSP100 can inject energy from ATP hydrolysis into the forceful unfolding of stable misfolded structures in proteins and convert them into unstable intermediates that can collapse into the native state, even under conditions inauspicious for that state. Aggregates and misfolded proteins may also be forcefully unfolded and degraded by chaperone-gated endo-cellular proteases, and in eukaryotes also by chaperone-mediated autophagy, paving the way for their replacement by new, unaltered functional proteins. The greater energy cost of degrading and replacing a polypeptide, with respect to the cost of its chaperone-mediated repair represents a thermodynamic dilemma: some easily repairable proteins are better to be processed by chaperones, while it can be wasteful to uselessly try recover overly compromised molecules, which should instead be degraded and replaced. Evolution has solved this conundrum by creating a host of unfolding chaperones and degradation machines and by tuning their cellular amounts and activity rates.
Keywords
chaperones, protein degradation, protein repair, proteostasis, thermodynamics
Pubmed
Web of science
Open Access
Yes
Create date
26/11/2021 19:33
Last modification date
03/12/2021 7:39
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