Reversible 26S proteasome disassembly upon mitochondrial stress

Nurit Livnat-Levanon, E. Kévei, Oded Kleifeld, Daria Krutauz, Alexandra Segref, Teresa Rinaldi, Zoi Erpapazoglou, Mickael Cohen, Noa Reis, Thorsten Hoppe, MichaelH Glickman

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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 invivo and invitro 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.

Original languageEnglish
Pages (from-to)1371-1380
Number of pages10
JournalCell Reports
Volume7
Issue number5
DOIs
Publication statusPublished - Jun 12 2014

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Oxidative stress
Proteasome Endopeptidase Complex
Reactive Oxygen Species
Oxidative Stress
Ubiquitinated Proteins
Holoenzymes
Eukaryotic Cells
Substrates
Ubiquitin
Proteolysis
Cysteine
Antioxidants
Aging of materials
Degradation
Oxidation
Defects
ATP dependent 26S protease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Livnat-Levanon, N., Kévei, E., Kleifeld, O., Krutauz, D., Segref, A., Rinaldi, T., ... Glickman, M. (2014). Reversible 26S proteasome disassembly upon mitochondrial stress. Cell Reports, 7(5), 1371-1380. https://doi.org/10.1016/j.celrep.2014.04.030

Reversible 26S proteasome disassembly upon mitochondrial stress. / Livnat-Levanon, Nurit; Kévei, E.; Kleifeld, Oded; Krutauz, Daria; Segref, Alexandra; Rinaldi, Teresa; Erpapazoglou, Zoi; Cohen, Mickael; Reis, Noa; Hoppe, Thorsten; Glickman, MichaelH.

In: Cell Reports, Vol. 7, No. 5, 12.06.2014, p. 1371-1380.

Research output: Contribution to journalArticle

Livnat-Levanon, N, Kévei, E, Kleifeld, O, Krutauz, D, Segref, A, Rinaldi, T, Erpapazoglou, Z, Cohen, M, Reis, N, Hoppe, T & Glickman, M 2014, 'Reversible 26S proteasome disassembly upon mitochondrial stress', Cell Reports, vol. 7, no. 5, pp. 1371-1380. https://doi.org/10.1016/j.celrep.2014.04.030
Livnat-Levanon N, Kévei E, Kleifeld O, Krutauz D, Segref A, Rinaldi T et al. Reversible 26S proteasome disassembly upon mitochondrial stress. Cell Reports. 2014 Jun 12;7(5):1371-1380. https://doi.org/10.1016/j.celrep.2014.04.030
Livnat-Levanon, Nurit ; Kévei, E. ; Kleifeld, Oded ; Krutauz, Daria ; Segref, Alexandra ; Rinaldi, Teresa ; Erpapazoglou, Zoi ; Cohen, Mickael ; Reis, Noa ; Hoppe, Thorsten ; Glickman, MichaelH. / Reversible 26S proteasome disassembly upon mitochondrial stress. In: Cell Reports. 2014 ; Vol. 7, No. 5. pp. 1371-1380.
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