Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Aug 1;3(8):a004374.
doi: 10.1101/cshperspect.a004374.

Cellular strategies of protein quality control

Bryan Chen  1 , Marco Retzlaff, Thomas Roos, Judith Frydman
Affiliations
Review

Cellular strategies of protein quality control

Bryan Chen et al. Cold Spring Harb Perspect Biol. .

Abstract

Eukaryotic cells must contend with a continuous stream of misfolded proteins that compromise the cellular protein homeostasis balance and jeopardize cell viability. An elaborate network of molecular chaperones and protein degradation factors continually monitor and maintain the integrity of the proteome. Cellular protein quality control relies on three distinct yet interconnected strategies whereby misfolded proteins can either be refolded, degraded, or delivered to distinct quality control compartments that sequester potentially harmful misfolded species. Molecular chaperones play a critical role in determining the fate of misfolded proteins in the cell. Here, we discuss the spatial and temporal organization of cellular quality control strategies and their implications for human diseases linked to protein misfolding and aggregation.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Cellular strategies to maintain protein homeostasis. Cells have evolved distinct yet interconnected cellular strategies to maintain protein homeostasis. Each strategy presents advantages and drawbacks. Misfolded proteins can either be refolded, degraded, or delivered to distinct quality control compartments that sequester potentially deleterious species. These strategies are all assisted by molecular chaperones that ensure the system remains balanced. Failure of the cellular strategies can tip the protein homeostasis balance and lead to a decrease in cell viability.
Figure 2.
Figure 2.
Distinct quality control compartments in eukaryotic cells. Quality control substrates can be sequestered into two spatial distinct compartments, the JUNQ and the IPOD. Misfolded, ubiquitinated proteins are delivered to the JUNQ, where they can be either degraded by the 26S proteasome or refolded with the assistance of chaperones, such as Hsp104. Insoluble misfolded proteins can also be terminally sequestered in the IPOD. The IPOD may be linked to the autophagy pathway based on its colocalization with Atg8. The molecular chaperone Hsp104 is also sequestered in the IPOD.
See this image and copyright information in PMC

References

    1. Aguilaniu H, Gustafsson L, Rigoulet M, Nystrom T 2003. Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science 299: 1751–1753 - PubMed
    1. Akerfelt M, Morimoto RI, Sistonen L 2010. Heat shock factors: Integrators of cell stress, development and lifespan. Nat Rev Mol Cell Biol 11: 545–555 - PMC - PubMed
    1. Albanese V, Yam AY, Baughman J, Parnot C, Frydman J 2006. Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells. Cell 124: 75–88 - PubMed
    1. Alberti S, Demand J, Esser C, Emmerich N, Schild H, Hohfeld J 2002. Ubiquitylation of BAG-1 suggests a novel regulatory mechanism during the sorting of chaperone substrates to the proteasome. J Biol Chem 277: 45920–45927 - PubMed
    1. An S, Kumar R, Sheets ED, Benkovic SJ 2008. Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science 320: 103–106 - PubMed

LinkOut - more resources