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

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 lab...

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Bibliographic Details
Published in:	Nature communications 2018-04, Vol.9 (1), p.1581-16, Article 1581
Main Authors:	van der Reest, Jiska, Lilla, Sergio, Zheng, Liang, Zanivan, Sara, Gottlieb, Eyal
Format:	Article
Language:	eng
Subjects:	Adaptation, Physiological Animal models Animals Cells, Cultured Cysteine Cysteine - chemistry Cysteine - metabolism Fumarate Hydratase - genetics Hydrogen Peroxide - metabolism Iodoacetamide - chemistry Isotope Labeling Kidney - metabolism Kidneys Labelling Male Mass spectrometry Mass spectroscopy Metabolism Mice Mice, Knockout Organs Oxidation Oxidation-Reduction Oxidative stress Oxidative Stress - physiology Proteins Proteome - analysis Proteome - chemistry Proteomes Proteomics - methods Reactive oxygen species Scale (corrosion) Sensitivity Sensitivity analysis Signal transduction Stable isotopes Workflow
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Summary:	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.
ISSN:	2041-1723 2041-1723