Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism

The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H S has been shown to persulfidate redox sensitive cysteine residues resulting in an H S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexi...

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Veröffentlicht in:Molecular & cellular proteomics 2020-05, Vol.19 (5), p.852
Hauptverfasser: Gao, Xing-Huang, Li, Ling, Parisien, Marc, Wu, Jing, Bederman, Ilya, Gao, Zhaofeng, Krokowski, Dawid, Chirieleison, Steven M, Abbott, Derek, Wang, Benlian, Arvan, Peter, Cameron, Mark, Chance, Mark, Willard, Belinda, Hatzoglou, Maria
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Sprache:eng
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Zusammenfassung:The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H S has been shown to persulfidate redox sensitive cysteine residues resulting in an H 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 H 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 (RTS ). We propose that the RTS from S-glutathioinylation to S-persulfidation is a potential mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress.
ISSN:1535-9484
DOI:10.1074/mcp.RA119.001910