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

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

Author information

1
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States.
2
Department of Pediatrics, Case Western Reserve University, Cleveland, United States.
3
Department of Pharmacology, Case Western Reserve University, Cleveland, United States.
4
Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
5
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States.
6
Mass Spectrometry Laboratory for Protein Sequencing, Lerner Research Institute, Cleveland Clinic, Cleveland, United States.
7
Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, United States.
8
Center for Synchotron Biosciences, School of Medicine, Case Western Reserve University, Cleveland, United States.
9
Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, United States.
10
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, United States.
11
Department of Medicine, Division of Hematology/Oncology, School of Medicine, Case Western Reserve University, Cleveland, United States.

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.

KEYWORDS:

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

PMID:
26595448
PMCID:
PMC4733038
DOI:
10.7554/eLife.10067
[Indexed for MEDLINE]
Free PMC Article

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