title: Reversible 26S proteasome disassembly upon mitochondrial stress.
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 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.
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Livnat-Levanon
authors.affiliation: Institute for Genetics, University of Cologne, Cologne 50674, Germany.
authors.forename: Éva
authors.initials: É
authors.lastname: Kevei
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; Department of Biochemistry and Molecular Biology, Faculty of Health Sciences, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Oded
authors.initials: O
authors.lastname: Kleifeld
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Daria
authors.initials: D
authors.lastname: Krutauz
authors.affiliation: Institute for Genetics, University of Cologne, Cologne 50674, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Segref
authors.affiliation: Department of Biology and Biotechnology, University of Rome "La Sapienza," Rome 00185, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rinaldi
authors.affiliation: Centre National de la Recherche Scientifique, UMR8226, IBPC, and Sorbonne Universités, UPMC, UMR8226, LBMCE, 75005 Paris, France.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Erpapazoglou
authors.affiliation: Centre National de la Recherche Scientifique, UMR8226, IBPC, and Sorbonne Universités, UPMC, UMR8226, LBMCE, 75005 Paris, France.
authors.forename: Mickael
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Reis
authors.affiliation: Institute for Genetics, University of Cologne, Cologne 50674, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hoppe
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. Electronic address: glickman@tx.technion.ac.il.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Glickman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003545:Cysteine / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055503:Protein Multimerization; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D003545:Cysteine