Deletion of DJ-1 in rats affects protein abundance and mitochondrial function at the synapse

Sci Rep. 2020 Aug 13;10(1):13719. doi: 10.1038/s41598-020-70486-0.


DJ-1 is a multifunctional protein affecting different biological and cellular processes. In addition, DJ-1 has roles in regulating mitochondrial function. Loss-of-function mutations in DJ-1 were found to cause an autosomal recessive form of Parkinson's disease. One of the main pathological features of PD is loss of dopamine neurons in the nigrostriatal pathway. DJ-1 knockout (KO) rats exhibit progressive nigral neurodegeneration with about 50% dopaminergic cell loss at 8 months of age. In order to assess the effects of DJ-1 deficiency on neuronal mitochondria prior to neuron loss, we performed proteomic analysis of synaptic mitochondria isolated from the striatum, the location of nigrostriatal pathway nerve terminals, of 3-month-old DJ-1 KO rats. In total, 371 mitochondrial proteins were quantified, and of these 76 were differentially expressed in DJ-1 KO rats. Proteins perturbed by the loss of DJ-1 were involved in several mitochondrial functional pathways, including the tricarboxylic acid cycle and electron transport chain. Thus, synaptic mitochondrial respiration was measured and showed a significant change due to DJ-1 deficiency. The dataset generated here highlights the role of synaptic mitochondria in PD associated with DJ-1. This study improves our understanding of DJ-1 effects in a complex tissue environment and the synaptic mitochondrial changes that accompany its loss.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Respiration
  • Corpus Striatum / metabolism*
  • Dopaminergic Neurons / metabolism*
  • Gene Deletion*
  • Male
  • Mitochondria / physiology*
  • Protein Deglycase DJ-1 / deficiency*
  • Protein Deglycase DJ-1 / genetics
  • Proteome / metabolism*
  • Rats
  • Synapses / physiology*


  • Proteome
  • PARK7 protein, rat
  • Protein Deglycase DJ-1