Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis

Bernadette Carroll, Elsje G. Otten, DIego Manni, Rhoda Stefanatos, Fiona M. Menzies, Graham R. Smith, Diana Jurk, Niall Kenneth, Simon Wilkinson, Joao Passos, Johannes Attems, Elizabeth A. Veal, Elisa Teyssou, Danielle Seilhean, Stéphanie Millecamps, Eeva Liisa Eskelinen, Agnieszka K. Bronowska, David C. Rubinsztein, Alberto Sanz, Viktor I. Korolchuk

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival.

Original languageEnglish (US)
Article number256
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

Fingerprint

homeostasis
Autophagy
Oxidation-Reduction
Homeostasis
Oxidative stress
proteins
Oxidation
vertebrates
oxidation
Cysteine
cysteine
Chemical activation
Proteins
activation
Pathology
Drosophila
Vertebrates
pathology
Oxidative Stress
organisms

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Carroll, B., Otten, E. G., Manni, DI., Stefanatos, R., Menzies, F. M., Smith, G. R., ... Korolchuk, V. I. (2018). Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis. Nature communications, 9(1), [256]. https://doi.org/10.1038/s41467-017-02746-z

Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis. / Carroll, Bernadette; Otten, Elsje G.; Manni, DIego; Stefanatos, Rhoda; Menzies, Fiona M.; Smith, Graham R.; Jurk, Diana; Kenneth, Niall; Wilkinson, Simon; Passos, Joao; Attems, Johannes; Veal, Elizabeth A.; Teyssou, Elisa; Seilhean, Danielle; Millecamps, Stéphanie; Eskelinen, Eeva Liisa; Bronowska, Agnieszka K.; Rubinsztein, David C.; Sanz, Alberto; Korolchuk, Viktor I.

In: Nature communications, Vol. 9, No. 1, 256, 01.12.2018.

Research output: Contribution to journalArticle

Carroll, B, Otten, EG, Manni, DI, Stefanatos, R, Menzies, FM, Smith, GR, Jurk, D, Kenneth, N, Wilkinson, S, Passos, J, Attems, J, Veal, EA, Teyssou, E, Seilhean, D, Millecamps, S, Eskelinen, EL, Bronowska, AK, Rubinsztein, DC, Sanz, A & Korolchuk, VI 2018, 'Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis', Nature communications, vol. 9, no. 1, 256. https://doi.org/10.1038/s41467-017-02746-z
Carroll B, Otten EG, Manni DI, Stefanatos R, Menzies FM, Smith GR et al. Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis. Nature communications. 2018 Dec 1;9(1). 256. https://doi.org/10.1038/s41467-017-02746-z
Carroll, Bernadette ; Otten, Elsje G. ; Manni, DIego ; Stefanatos, Rhoda ; Menzies, Fiona M. ; Smith, Graham R. ; Jurk, Diana ; Kenneth, Niall ; Wilkinson, Simon ; Passos, Joao ; Attems, Johannes ; Veal, Elizabeth A. ; Teyssou, Elisa ; Seilhean, Danielle ; Millecamps, Stéphanie ; Eskelinen, Eeva Liisa ; Bronowska, Agnieszka K. ; Rubinsztein, David C. ; Sanz, Alberto ; Korolchuk, Viktor I. / Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis. In: Nature communications. 2018 ; Vol. 9, No. 1.
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