Sulfhydration mediates neuroprotective actions of parkin

M. Scott Vandiver, Bindu D. Paul, Risheng Xu, Senthilkumar Karuppagounder, Feng Rao, Adele M. Snowman, Han Seok Ko, Yun Il Lee, Valina L. Dawson, Ted M. Dawson, Nilkantha Sen, Solomon H. Snyder

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Abstract

Increases in S-nitrosylation and inactivation of the neuroprotective ubiquitin E3 ligase, parkin, in the brains of patients with Parkinson's disease are thought to be pathogenic and suggest a possible mechanism linking parkin to sporadic Parkinson's disease. Here we demonstrate that physiologic modification of parkin by hydrogen sulfide, termed sulfhydration, enhances its catalytic activity. Sulfhydration sites are identified by mass spectrometry analysis and are investigated by site-directed mutagenesis. Parkin sulfhydration is markedly depleted in the brains of patients with Parkinson's disease, suggesting that this loss may be pathologic. This implies that hydrogen sulfide donors may be therapeutic.

Original languageEnglish (US)
Article number1626
JournalNature Communications
Volume4
DOIs
Publication statusPublished - Apr 11 2013

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Vandiver, M. S., Paul, B. D., Xu, R., Karuppagounder, S., Rao, F., Snowman, A. M., ... Snyder, S. H. (2013). Sulfhydration mediates neuroprotective actions of parkin. Nature Communications, 4, [1626]. https://doi.org/10.1038/ncomms2623