1. Biochemistry and Chemical Biology
  2. Cell Biology
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Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the Integrated Stress Response

  1. Xing-Huang Gao
  2. Dawid Krokowski
  3. Bo-Jhih Guan
  4. Ilya Bederman
  5. Mithu Majumder
  6. Marc Parisien
  7. Luda Diatchenko
  8. Omer Kabil
  9. Belinda Willard
  10. Ruma Banerjee
  11. Benlian Wang
  12. Gurkan Bebek
  13. Charles R Evans
  14. Paul L Fox
  15. Stanton L Gerson
  16. Charles Hoppel
  17. Ming Liu
  18. Peter Arvan
  19. Maria Hatzoglou  Is a corresponding author
  1. Case Western Reserve University, United States
  2. McGill University, Canada
  3. University of Michigan Medical School, United States
  4. Cleveland Clinic Lerner Research Institute, United States
Research Article
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Cite this article as: eLife 2015;4:e10067 doi: 10.7554/eLife.10067

Abstract

The sulfhydration of cysteine residues in proteins is an important mechanism involved in diverse biological processes. We have developed a proteomics approach to quantitatively profile the changes of sulfhydrated cysteines in biological systems. Bioinformatics analysis revealed that sulfhydrated cysteines are part of a wide range of biological functions. In pancreatic β cells exposed to endoplasmic reticulum (ER) stress, elevated H2S promotes the sulfhydration of enzymes in energy metabolism and stimulates glycolytic flux. We propose that transcriptional and translational reprogramming by the Integrated Stress Response (ISR) in pancreatic β cells is coupled to metabolic alternations triggered by sulfhydration of key enzymes in intermediary metabolism.

Article and author information

Author details

  1. Xing-Huang Gao

    Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Dawid Krokowski

    Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Bo-Jhih Guan

    Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ilya Bederman

    Department of Pediatrics, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mithu Majumder

    Department of Pharmacology, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Marc Parisien

    Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Luda Diatchenko

    Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Omer Kabil

    Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Belinda Willard

    Mass Spectrometry Laboratory for Protein Sequencing, Cleveland Clinic Lerner Research Institute, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Ruma Banerjee

    Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Benlian Wang

    Center for Proteomics and Bioinformatics,Center for Synchrotron Biosciences, School of Medicine, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Gurkan Bebek

    Center for Proteomics and Bioinformatics, Center for Synchrotron Biosciences, School of Medicine, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Charles R Evans

    Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Paul L Fox

    Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Stanton L Gerson

    Department of Medicine, Division of Hematology/Oncology, School of Medicine, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Charles Hoppel

    Department of Pharmacology, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Ming Liu

    Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Peter Arvan

    Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Maria Hatzoglou

    Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States
    For correspondence
    mxh8@case.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Experimental protocols were approved by the Case Western Reserve University Institutional Animal Care and Use Committee.

Human subjects: Human Islet Study-Institutional review board approval for research use of isolated human islets was obtained from the University of Michigan (IRB number 2014-0069). Human islets were isolated from previously healthy, nondiabetic organ donors by the University of Chicago Transplant Center. Three independent human islet batches from two male donors aged 20 and 58 and one female donor aged 48 were used in this study.

Reviewing Editor

  1. Ben Cravatt, The Scripps Research Institute, United States

Publication history

  1. Received: July 14, 2015
  2. Accepted: November 16, 2015
  3. Accepted Manuscript published: November 23, 2015 (version 1)
  4. Version of Record published: January 18, 2016 (version 2)

Copyright

© 2015, Gao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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