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Review
. 2011 Aug 1;3(8):a004374.
doi: 10.1101/cshperspect.a004374.

Cellular strategies of protein quality control

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.

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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.

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