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 ORCID: 0000-0001-8528-1021, Wilkinson, Simon, Passos, Joao F
et al (show 10 more authors) (2018) Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis. Nature Communications, 9 (1). 256-.

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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.

Item Type: Article
Uncontrolled Keywords: Cells, Cultured, Hela Cells, Animals, Mice, Knockout, Humans, Drosophila melanogaster, Hydrogen Peroxide, Reactive Oxygen Species, Oxidants, Cell Survival, Amino Acid Sequence, Sequence Homology, Amino Acid, Oxidation-Reduction, Autophagy, HEK293 Cells, Sequestosome-1 Protein, Proteostasis
Depositing User: Symplectic Admin
Date Deposited: 21 Jul 2020 08:23
Last Modified: 18 Jan 2023 23:40
DOI: 10.1038/s41467-017-02746-z
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3094659