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 |
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Hauptverfasser: | , , , , , , , , , , , , , , |
Format: | Artikel |
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. |
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ISSN: | 1535-9484 |
DOI: | 10.1074/mcp.RA119.001910 |