title: Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response.
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.
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States.
authors.forename: Xing-Huang
authors.initials: XH
authors.lastname: Gao
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States.
authors.forename: Dawid
authors.initials: D
authors.lastname: Krokowski
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States.
authors.forename: Bo-Jhih
authors.initials: BJ
authors.lastname: Guan
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, United States.
authors.forename: Ilya
authors.initials: I
authors.lastname: Bederman
authors.affiliation: Department of Pharmacology, Case Western Reserve University, Cleveland, United States.
authors.forename: Mithu
authors.initials: M
authors.lastname: Majumder
authors.affiliation: Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Parisien
authors.affiliation: Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Omer
authors.initials: O
authors.lastname: Kabil
authors.affiliation: Mass Spectrometry Laboratory for Protein Sequencing, Lerner Research Institute, Cleveland Clinic, Cleveland, United States.
authors.forename: Belinda
authors.initials: B
authors.lastname: Willard
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Ruma
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, United States.|Center for Synchotron Biosciences, School of Medicine, Case Western Reserve University, Cleveland, United States.
authors.forename: Benlian
authors.initials: B
authors.lastname: Wang
authors.affiliation: Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, United States.|Center for Synchotron Biosciences, School of Medicine, Case Western Reserve University, Cleveland, United States.
authors.forename: Gurkan
authors.initials: G
authors.lastname: Bebek
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Evans
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, United States.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Fox
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, School of Medicine, Case Western Reserve University, Cleveland, United States.
authors.forename: Stanton L
authors.initials: SL
authors.lastname: Gerson
authors.affiliation: Department of Pharmacology, Case Western Reserve University, Cleveland, United States.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hoppel
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Arvan
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Hatzoglou
mesh_terms: D000818:Animals; D019295:Computational Biology; D003545:Cysteine / Q000378:metabolism*; D005786:Gene Expression Regulation; D006862:Hydrogen Sulfide / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D008810:Mice, Inbred C57BL; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis; D013312:Stress, Physiological
chemical_list: D020543:Proteome; D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: Cystathionine gamma-lyase (CSE); Integrated Stress Response; biochemistry; cell biology; hydrogen sulfide; metabolic reprogramming; mouse; protein sulfhydration; quantitative proteomics