Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response
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
Affiliations
Xing-Huang Gao
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States
Dawid Krokowski
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States
Bo-Jhih Guan
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States
Ilya Bederman
Department of Pediatrics, Case Western Reserve University, Cleveland, United States
Mithu Majumder
Department of Pharmacology, Case Western Reserve University, Cleveland, United States
Marc Parisien
Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada
Luda Diatchenko
Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada
Omer Kabil
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States
Belinda Willard
Mass Spectrometry Laboratory for Protein Sequencing, Lerner Research Institute, Cleveland Clinic, Cleveland, United States
Ruma Banerjee
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States
Benlian Wang
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
Gurkan Bebek
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
Charles R. Evans
Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, United States
Paul L. Fox
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, United States
Stanton L. Gerson
Department of Medicine, Division of Hematology/Oncology, School of Medicine, Case Western Reserve University, Cleveland, United States
Charles L. Hoppel
Department of Pharmacology, Case Western Reserve University, Cleveland, United States
Ming Liu
Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, United States
Peter Arvan
Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, United States
Maria Hatzoglou
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States
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.
