Protein quality control under oxidative stress conditions

J Mol Biol. 2015 Apr 10;427(7):1549-63. doi: 10.1016/j.jmb.2015.02.014. Epub 2015 Feb 16.


Accumulation of reactive oxygen and chlorine species (RO/CS) is generally regarded to be a toxic and highly undesirable event, which serves as contributing factor in aging and many age-related diseases. However, it is also put to excellent use during host defense, when high levels of RO/CS are produced to kill invading microorganisms and regulate bacterial colonization. Biochemical and cell biological studies of how bacteria and other microorganisms deal with RO/CS have now provided important new insights into the physiological consequences of oxidative stress, the major targets that need protection, and the cellular strategies employed by organisms to mitigate the damage. This review examines the redox-regulated mechanisms by which cells maintain a functional proteome during oxidative stress. We will discuss the well-characterized redox-regulated chaperone Hsp33, and we will review recent discoveries demonstrating that oxidative stress-specific activation of chaperone function is a much more widespread phenomenon than previously anticipated. New members of this group include the cytosolic ATPase Get3 in yeast, the Escherichia coli protein RidA, and the mammalian protein α2-macroglobulin. We will conclude our review with recent evidence showing that inorganic polyphosphate (polyP), whose accumulation significantly increases bacterial oxidative stress resistance, works by a protein-like chaperone mechanism. Understanding the relationship between oxidative and proteotoxic stresses will improve our understanding of both host-microbe interactions and how mammalian cells combat the damaging side effects of uncontrolled RO/CS production, a hallmark of inflammation.

Keywords: N-chlorination; disulfide bond formation; molecular chaperone; oxidative stress; protein aggregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism
  • Chlorine Compounds / toxicity
  • Humans
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Protein Aggregates / physiology
  • Protein Unfolding
  • Proteins / chemistry
  • Proteins / metabolism*
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology


  • Anti-Infective Agents
  • Chlorine Compounds
  • Protein Aggregates
  • Proteins
  • Reactive Oxygen Species