Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response

• DOI: 10.7554/elife.10067
• Publication Date: 2015-11-23T12:32:35Z
• Authors: Xing-Huang Gao; Dawid Krokowski; Bo-Jhih Guan; Ilya Bederman; Mithu Majumder; Marc Parisien; Luda Diatchenko; Omer Kabil; Belinda Willard; Ruma Banerjee; Benlian Wang; Gurkan Bebek; Charles R. Evans; Paul L. Fox; Stanton L. Gerson; Charles L. Hoppel; Ming Liu; Peter Arvan; Maria Hatzoglou
• Keywords: quantitative proteomics; 0301 basic medicine; Cell biology; Proteome; QH301-705.5; Science; hydrogen sulfide; 610; Cystathionine gamma-lyase (CSE); Integrated Stress Response; Biochemistry; 03 medical and health sciences; Stress, Physiological; protein sulfhydration; Protein sulfhydration; metabolic reprogramming; Animals; Cysteine; Hydrogen Sulfide; Biology (General); Hydrogen sulfide; Q; R; Computational Biology; Mice, Inbred C57BL; Gene Expression Regulation; Medicine; Protein Processing, Post-Translational; Metabolic Networks and Pathways

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.