Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the Integrated Stress Response
- Case Western Reserve University, United States
- McGill University, Canada
- University of Michigan Medical School, United States
- Cleveland Clinic Lerner Research Institute, United States
- Cited 77
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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.
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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
- Ben Cravatt, The Scripps Research Institute, United States
Publication history
- Received: July 14, 2015
- Accepted: November 16, 2015
- Accepted Manuscript published: November 23, 2015 (version 1)
- 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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