Reversible 26S Proteasome Disassembly upon Mitochondrial Stress

Nurit Livnat-Levanon (1) , Eva Kevei (2) , Oded Kleifeld (3, 1) , Daria Krutauz (1) , Alexandra Segref (2) , Teresa Rinaldi (4) , Zoi Erpapazoglou (5) , Mickael Cohen (5) , Noa Reis (1) , Thorsten Hoppe (2) , Michael H Glickman (1)

1 Technion - Israel Institute of Technology [Haifa]
2 Universität zu Köln = University of Cologne
3 Monash University [Clayton]
4 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
5 LBMCE - Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes

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, mito-chondrial 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 sub-strate turnover also resumes after treatment with antioxidants. Reversible attenuation of 26S protea-some 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.

Domaines: Biologie cellulaire

Nurit Livnat-Levanon, Eva Kevei, Oded Kleifeld, Daria Krutauz, Alexandra Segref, et al.. Reversible 26S Proteasome Disassembly upon Mitochondrial Stress. Cell Reports, 2014, 7 (5), pp.1371-1380. ⟨10.1016/j.celrep.2014.04.030⟩. ⟨hal-01311781⟩