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

Author

Listed:
  • Jiska Reest

    (Cancer Research UK Beatson Institute)

  • Sergio Lilla

    (Cancer Research UK Beatson Institute)

  • Liang Zheng

    (Cancer Research UK Beatson Institute
    Shanghai Jiao Tong University School of Medicine)

  • Sara Zanivan

    (Cancer Research UK Beatson Institute
    University of Glasgow)

  • Eyal Gottlieb

    (Cancer Research UK Beatson Institute
    University of Glasgow
    Technion - Israel Institute of Technology)

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.

Suggested Citation

  • Jiska Reest & Sergio Lilla & Liang Zheng & Sara Zanivan & Eyal Gottlieb, 2018. "Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04003-3
    DOI: 10.1038/s41467-018-04003-3
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    1. Maithily S. Nanadikar & Ana M. Vergel Leon & Jia Guo & Gijsbert J. Belle & Aline Jatho & Elvina S. Philip & Astrid F. Brandner & Rainer A. Böckmann & Runzhu Shi & Anke Zieseniss & Carla M. Siemssen & , 2023. "IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Pavan S. Upadhyayula & Dominique M. Higgins & Angeliki Mela & Matei Banu & Athanassios Dovas & Fereshteh Zandkarimi & Purvi Patel & Aayushi Mahajan & Nelson Humala & Trang T. T. Nguyen & Kunal R. Chau, 2023. "Dietary restriction of cysteine and methionine sensitizes gliomas to ferroptosis and induces alterations in energetic metabolism," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Emma Martell & Helgi Kuzmychova & Esha Kaul & Harshal Senthil & Subir Roy Chowdhury & Ludivine Coudière Morrison & Agnes Fresnoza & Jamie Zagozewski & Chitra Venugopal & Chris M. Anderson & Sheila K. , 2023. "Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 medulloblastoma," Nature Communications, Nature, vol. 14(1), pages 1-26, December.

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