Sulfhydration mediates neuroprotective actions of parkin

Nat Commun. 2013;4:1626. doi: 10.1038/ncomms2623.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Catalysis
  • Hydrogen Sulfide / pharmacology
  • Mass Spectrometry
  • Molecular Sequence Data
  • Neuroprotective Agents / metabolism*
  • Nitroso Compounds / metabolism
  • Sulfhydryl Compounds / metabolism*
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitin-Protein Ligases / physiology*

Substances

  • Neuroprotective Agents
  • Nitroso Compounds
  • Sulfhydryl Compounds
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Hydrogen Sulfide