Monoamine oxidase-A knockdown in human neuroblastoma cells reveals protection against mitochondrial toxins

FASEB J. 2014 Jan;28(1):218-29. doi: 10.1096/fj.13-235481. Epub 2013 Sep 19.


The study examined how the mitochondrial enzyme monoamine oxidase-A (MAO-A), which produces hydrogen peroxide as a catalytic by-product, influences death and survival mechanisms. Targeted microRNA (miRNA) was used to stably knock down MAO-A mRNA, protein, and catalytic activity by 60-70% in SH-SY5Y human neuroblastoma cells. The effects of MAO-A knockdown (KD) on ATP, oxidative stress, electron transport chain, and survival following exposure to mitochondrial toxins were assessed. In control cells, complex I inhibition resulted in caspase-mediated cell death linked with ROS production and reduced ATP, followed by up-regulation of MAO-A mRNA, protein, and enzyme activity levels. Inhibition of complex III and IV resulted in a similar increase in MAO-A expression, while up-regulation of MAO-A was lower following complex II inhibition. MAO-A KD decreased basal reactive oxygen species levels by 50% and increased levels of ATP and reduced glutathione and Bcl-2. MAO-A KD specifically increased the activity of complex I but had no effect on complex II-IV activities. Furthermore, MAO-A KD protected against inhibitors of complex I, III, and IV. In summary, endogenous MAO-A levels influence mitochondrial function, notably complex I activity, and MAO-A may be a target for protection against neurodegenerative conditions that involve oxidative stress and mitochondrial dysfunction as underlying pathogenic factors.

Keywords: Parkinson's disease; electron transport chain; neurodegeneration; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cell Line, Tumor
  • Humans
  • MicroRNAs / genetics
  • Mitochondria / metabolism
  • Monoamine Oxidase / genetics
  • Monoamine Oxidase / metabolism*
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Reactive Oxygen Species / metabolism


  • MicroRNAs
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • Monoamine Oxidase