Reversible 26S proteasome disassembly upon mitochondrial stress

Cell Rep. 2014 Jun 12;7(5):1371-1380. doi: 10.1016/j.celrep.2014.04.030. Epub 2014 May 22.


In eukaryotic cells, proteasomes exist primarily as 26S holoenzymes, the most efficient configuration for ubiquitinated protein degradation. Here, we show that acute oxidative stress caused by environmental insults or mitochondrial defects results in rapid disassembly of 26S proteasomes into intact 20S core and 19S regulatory particles. Consequently, polyubiquitinated substrates accumulate, mitochondrial networks fragment, and cellular reactive oxygen species (ROS) levels increase. Oxidation of cysteine residues is sufficient to induce proteasome disassembly, and spontaneous reassembly from existing components is observed both in vivo and in vitro upon reduction. Ubiquitin-dependent substrate turnover also resumes after treatment with antioxidants. Reversible attenuation of 26S proteasome activity induced by acute mitochondrial or oxidative stress may be a short-term response distinct from adaptation to long-term ROS exposure or changes during aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Caenorhabditis elegans / metabolism
  • Cell Line
  • Cricetinae
  • Cysteine / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Oxidative Stress*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Multimerization*
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Ubiquitin / metabolism


  • Antioxidants
  • Reactive Oxygen Species
  • Ubiquitin
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease
  • Cysteine