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.

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. © 2014 The Authors.

Reversible 26S Proteasome Disassembly upon Mitochondrial Stress / Nurit Livnat, Levanon; Eva, Kevei; Oded, Kleifeld; Daria, Krutauz; Alexandra, Segref; Rinaldi, Teresa; Zoi, Erpapazoglou; Mickael, Cohen; Noa, Reis; Thorsten, Hoppe; Michael H., Glickman. - In: CELL REPORTS. - ISSN 2211-1247. - ELETTRONICO. - 7:5(2014), pp. 1371-1380. [10.1016/j.celrep.2014.04.030]

Reversible 26S Proteasome Disassembly upon Mitochondrial Stress

RINALDI, Teresa;
2014

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.
2014
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. © 2014 The Authors.
proteasome; mitochondria; stress
01 Pubblicazione su rivista::01a Articolo in rivista
Reversible 26S Proteasome Disassembly upon Mitochondrial Stress / Nurit Livnat, Levanon; Eva, Kevei; Oded, Kleifeld; Daria, Krutauz; Alexandra, Segref; Rinaldi, Teresa; Zoi, Erpapazoglou; Mickael, Cohen; Noa, Reis; Thorsten, Hoppe; Michael H., Glickman. - In: CELL REPORTS. - ISSN 2211-1247. - ELETTRONICO. - 7:5(2014), pp. 1371-1380. [10.1016/j.celrep.2014.04.030]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/642398
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