Quantitative H2S-mediated Protein Sulfhydration Reveals Metabolic Reprogramming During the Integrated Stress Response

Elife. 2015 Nov 23;4:e10067. doi: 10.7554/eLife.10067.


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.

Keywords: Cystathionine gamma-lyase (CSE); Integrated Stress Response; biochemistry; cell biology; hydrogen sulfide; metabolic reprogramming; mouse; protein sulfhydration; quantitative proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computational Biology
  • Cysteine / metabolism*
  • Gene Expression Regulation*
  • Hydrogen Sulfide / metabolism*
  • Metabolic Networks and Pathways*
  • Mice, Inbred C57BL
  • Protein Processing, Post-Translational*
  • Proteome / analysis
  • Stress, Physiological*


  • Proteome
  • Cysteine
  • Hydrogen Sulfide