Sulfhydration mediates neuroprotective actions of parkin

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

Research output: Contribution to journalArticle

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
StatePublished - 2013

Fingerprint

Parkinson disease
Parkinson Disease
Hydrogen Sulfide
hydrogen sulfide
brain
Brain
mutagenesis
Mutagenesis
Ubiquitin-Protein Ligases
Site-Directed Mutagenesis
deactivation
Mass spectrometry
catalytic activity
Catalyst activity
Mass Spectrometry
mass spectroscopy
Therapeutics

ASJC Scopus subject areas

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

Cite this

Sulfhydration mediates neuroprotective actions of parkin. / Vandiver, M. Scott; Paul, Bindu; Xu, Risheng; Karuppagounder, Senthilkumar; Rao, Feng; Snowman, Adele M; Ko, Hanseok Seok; Il Lee, Yun; Dawson, Valina; Dawson, Ted M; Sen, Nilkantha; Snyder, Solomon H.

In: Nature Communications, Vol. 4, 1626, 2013.

Research output: Contribution to journalArticle

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AU - Vandiver, M. Scott

AU - Paul, Bindu

AU - Xu, Risheng

AU - Karuppagounder, Senthilkumar

AU - Rao, Feng

AU - Snowman, Adele M

AU - Ko, Hanseok Seok

AU - Il Lee, Yun

AU - Dawson, Valina

AU - Dawson, Ted M

AU - Sen, Nilkantha

AU - Snyder, Solomon H

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