Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress

van der Reest, J., Lilla, S., Zheng, L., Zanivan, S. and Gottlieb, E. (2018) Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress. Nature Communications, 9, 1581. (doi: 10.1038/s41467-018-04003-3) (PMID:29679077) (PMCID:PMC5910380)

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Abstract

Reactive oxygen species (ROS) are increasingly recognised as important signalling molecules through oxidation of protein cysteine residues. Comprehensive identification of redox-regulated proteins and pathways is crucial to understand ROS-mediated events. Here, we present stable isotope cysteine labelling with iodoacetamide (SICyLIA), a mass spectrometry-based workflow to assess proteome-scale cysteine oxidation. SICyLIA does not require enrichment steps and achieves unbiased proteome-wide sensitivity. Applying SICyLIA to diverse cellular models and primary tissues provides detailed insights into thiol oxidation proteomes. Our results demonstrate that acute and chronic oxidative stress causes oxidation of distinct metabolic proteins, indicating that cysteine oxidation plays a key role in the metabolic adaptation to redox stress. Analysis of mouse kidneys identifies oxidation of proteins circulating in biofluids, through which cellular redox stress can affect whole-body physiology. Obtaining accurate peptide oxidation profiles from complex organs using SICyLIA holds promise for future analysis of patient-derived samples to study human pathologies.

Item Type:Articles
Additional Information:This work was supported by Cancer Research UK grants A18278 (J.vdR., L.Z., E.G.), A17196 (S.L.), A12935 and the Stand Up to Cancer campaign for Cancer Research UK (S.Z.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:van der Reest, Jiska and Lilla, Dr Sergio and Zheng, Mr Liang and Zanivan, Professor Sara Rossana and Gottlieb, Professor Eyal
Authors: van der Reest, J., Lilla, S., Zheng, L., Zanivan, S., and Gottlieb, E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9: 1581
Publisher Policy:Reproduced under a Creative Commons License

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