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Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

Quality control against misfolded proteins in the cytosol: a network for cell survival

Hiroshi Kubota1

  • 1Department of Life Science, Faculty of Engineering and Resource Science, Akita University, Akita 010-8502, Japan. hkubota@ipc.akita-u.ac.jp

Journal of Biochemistry
|September 10, 2009
PubMed

Insights

Cellular protein quality control systems prevent toxicity from misfolded proteins, which cause diseases like neurodegeneration. These systems clear toxic protein monomers and aggregates through various pathways.

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Misfolded proteins accumulate and cause cellular toxicity, leading to diseases such as neurodegenerative disorders.
  • Exposed hydrophobic surfaces on misfolded proteins mediate aberrant interactions, disrupting normal cellular functions.
  • Cellular protein quality control (PQC) mechanisms are essential for maintaining proteostasis and preventing disease.

Purpose of the Study:

  • To review the critical roles of PQC pathways in managing misfolded proteins in the cytosol.
  • To highlight recent advancements in understanding the regulation of PQC networks.
  • To elucidate the mechanisms by which cells eliminate toxic protein species.

Main Methods:

  • This review synthesizes current literature on PQC pathways.
  • It examines the functions of molecular chaperones, the ubiquitin-proteasome system, and autophagy.
  • The role of microtubule-dependent transport in aggregate sequestration is discussed.

Main Results:

  • PQC pathways, including chaperone-mediated protein folding and degradation systems (ubiquitin-proteasome system, chaperone-mediated autophagy, macroautophagy-lysosome system), effectively remove misfolded proteins.
  • Molecular chaperones mask hydrophobic surfaces of misfolded monomers, directing them for degradation.
  • Microtubule-dependent transport sequesters soluble aggregates into inclusion bodies, preventing cellular damage.

Conclusions:

  • Effective removal of toxic protein monomers and aggregates relies on coordinated PQC pathways.
  • Regulation by stress-inducible factors, cochaperones, and cofactors is crucial for PQC efficiency.
  • Understanding PQC networks offers insights into preventing and treating protein misfolding diseases.

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