Sulfhydration mediates neuroprotective actions of parkin

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. The gasotransmitter hydrogen sulfide signals by sulfide modification of target proteins. Vandiver and colleagues study the sulfhydration of parkin by hydrogen sulfide and find that sulfhydration stimulates its activity, and that this activity is reduced in patients with Parkinson’s disease.

• Publication year

  2013

• Venue

  Nature Communications

• Publication date

  2013-03-18

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1038/ncomms2623PMID 23535647PMCID 3622945
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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