1. Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism.
- Author
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Gao XH, Li L, Parisien M, Wu J, Bederman I, Gao Z, Krokowski D, Chirieleison SM, Abbott D, Wang B, Arvan P, Cameron M, Chance M, Willard B, and Hatzoglou M
- Subjects
- Activating Transcription Factor 4 metabolism, Animals, Biological Assay, Biotin metabolism, Cell Line, Cysteine metabolism, Disulfides metabolism, Glycolysis, Hepatocytes metabolism, Humans, Hydrogen Sulfide metabolism, Insulin-Secreting Cells metabolism, Mass Spectrometry, Metabolic Flux Analysis, Mitochondria metabolism, Oxidation-Reduction, Proteome metabolism, Proteomics, Rats, Sulfides metabolism, Energy Metabolism, Sulfhydryl Compounds metabolism
- Abstract
The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H
2 S has been shown to persulfidate redox sensitive cysteine residues resulting in an H2 S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent in detecting cysteine modifications. Here we developed a TMT-based proteomics approach for selectively trapping and tagging cysteine persulfides in the cellular proteomes. We revealed the natural protein sulfhydrome of two human cell lines, and identified insulin as a novel substrate in pancreatic beta cells. Moreover, we showed that under oxidative stress conditions, increased H2 S can target enzymes involved in energy metabolism by switching specific cysteine modifications to persulfides. Specifically, we discovered a Redox Thiol Switch, from protein S-glutathioinylation to S-persulfidation (RTSGS ). We propose that the RTSGS from S-glutathioinylation to S-persulfidation is a potential mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress., (© 2020 Gao et al.)- Published
- 2020
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