Parkin deficiency accelerates consequences of mitochondrial DNA deletions and Parkinsonism

Lanying Song, Marissa McMackin, Andy Nguyen, Gino A Cortopassi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Parkinson's disease (PD) is a neurodegenerative condition caused by age-related death of dopaminergic (DA) neurons in the substantia nigra (SN). Mitochondrial DNA (mtDNA) deletions rise exponentially with age in humans and reach their highest levels approaching 60% in dopaminergic neurons of the substantia nigra and overlap with dying neurons. Parkin deletion causes Parkinsonism in humans, presumably through a decrease in mitochondrial quality control, but Parkin knockout mice do not have DA neurodegeneration. We crossed Parkin knockouts to the Twinkle-TG mouse in which mtDNA deletions are increased specifically in substantia nigra to determine the effect of increased deletion mutagenesis in the absence of mitochondrial quality control. These double-mutant ‘TwinkPark’ mice had 1, the highest mtDNA deletion concentration in SN; 2, the lowest mitochondrial function and membrane potential; 3, the most severe neurobehavioral deficits at 19 months; 4, the least dopaminergic neurons in the SN and lowest dopamine levels, i.e. Parkinsonism. This mouse model could provide novel insights into the pathomechanism by which a specific increase in mtDNA deletions with age contribute to dopaminergic neurodegeneration and Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)30-38
Number of pages9
JournalNeurobiology of Disease
StatePublished - Apr 1 2017


  • mtDNA deletion
  • Parkin deficiency
  • Parkinson's disease
  • Twinkle mutation

ASJC Scopus subject areas

  • Neurology


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