Distinct mechanisms of pathogenic DJ-1 mutations in mitochondrial quality control

Daniela Strobbe, Alexis A. Robinson, Kirsten Harvey, Lara Rossi, Caterina Ferraina, Valerio De Biase, Carlo Rodolfo, Robert J. Harvey, Michelangelo Campanella

Research output: Contribution to journalArticlepeer-review


The deglycase and chaperone protein DJ-1 is pivotal for cellular oxidative stress responses and mitochondrial quality control. Mutations in PARK7, encoding DJ-1, are associated with early-onset familial Parkinson’s disease and lead to pathological oxidative stress and/or disrupted protein degradation by the proteasome. The aim of this study was to gain insights into the pathogenic mechanisms of selected DJ-1 missense mutations, by characterizing protein–protein interactions, core parameters of mitochondrial function, quality control regulation via autophagy, and cellular death following dopamine accumulation. We report that the DJ-1M26I mutant influences DJ-1 interactions with SUMO-1, in turn enhancing removal of mitochondria and conferring increased cellular susceptibility to dopamine toxicity. By contrast, the DJ-1D149A mutant does not influence mitophagy, but instead impairs Ca2+ dynamics and free radical homeostasis by disrupting DJ-1 interactions with a mitochondrial accessory protein known as DJ-1-binding protein (DJBP/EFCAB6). Thus, individual DJ-1 mutations have different effects on mitochondrial function and quality control, implying mutation-specific pathomechanisms converging on impaired mitochondrial homeostasis.

Original languageEnglish
Pages (from-to)68
JournalFrontiers in Molecular Neuroscience
Publication statusPublished - Mar 15 2018


  • DJ-1
  • Mitochondria
  • Mitophagy
  • PARK7
  • SUMO-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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