Dopamine Oxidation Products as Mitochondrial Endotoxins, a Potential Molecular Mechanism for Preferential Neurodegeneration in Parkinson's Disease

ACS Chem Neurosci. 2018 Nov 21;9(11):2849-2858. doi: 10.1021/acschemneuro.8b00276. Epub 2018 Jul 3.


The preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta is responsible for the motor impairment associated with Parkinson's disease. Dopamine is a highly reactive molecule, which is usually stored inside synaptic vesicles where it is stabilized by the ambient low pH. However, free cytosolic dopamine can auto-oxidize, generating reactive oxygen species, and lead to the formation of toxic quinones. In the present work, we have analyzed the mechanisms through which the dysfunction of dopamine homeostasis could induce cell toxicity, by focusing in particular on the damage induced by dopamine oxidation products at the mitochondrial level. Our results indicate that dopamine derivatives affect mitochondrial morphology and induce mitochondrial membrane depolarization, leading to a reduction of ATP synthesis. Moreover, our results suggest that opening of the mitochondrial transition pore induced by dopamine-derived quinones may contribute to the specific Parkinson's disease-associated vulnerability of dopamine containing neurons.

Keywords: ATP synthase; Parkinson’s disease; dopamine; dopamine-derived quinones; mitochondria; permeability transition pore.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Dopamine / metabolism*
  • Dopaminergic Neurons
  • Endotoxins / metabolism
  • Endotoxins / pharmacology
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria, Liver / drug effects
  • Mitochondrial Membrane Transport Proteins / drug effects
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Permeability Transition Pore
  • Oxidation-Reduction
  • Parkinson Disease*
  • Pars Compacta
  • Quinones / pharmacology*
  • Rats
  • Reactive Oxygen Species / metabolism*


  • Endotoxins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Quinones
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • Dopamine