Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease

Lena F. Burbulla, Pingping Song, Joseph R. Mazzulli, Enrico Zampese, Yvette C. Wong, Sohee Jeon, David P. Santos, Judith Blanz, Carolin D. Obermaier, Chelsee Strojny, Jeffrey N. Savas, Evangelos Kiskinis, Xiaoxi Zhuang, Rejko Krüger, D. James Surmeier, Dimitri Krainc*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

390 Scopus citations


Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson’s disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and a-synuclein accumulation. This toxic cascade was observed in human, but not in mouse, PD neurons at least in part because of species-specific differences in dopamine metabolism. Increasing dopamine synthesis or a-synuclein amounts in mouse midbrain neurons recapitulated pathological phenotypes observed in human neurons. Thus, dopamine oxidation represents an important link between mitochondrial and lysosomal dysfunction in PD pathogenesis.

Original languageEnglish (US)
Pages (from-to)1255-1261
Number of pages7
Issue number6357
StatePublished - Sep 22 2017

ASJC Scopus subject areas

  • General


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