Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease

PLoS One. 2016 Jul 19;11(7):e0159209. doi: 10.1371/journal.pone.0159209. eCollection 2016.


Friedreich's ataxia (FRDA), the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin deficiency-induced phenotypes. Taken together, these results demonstrate that the metal dysregulation in FRDA includes other metals besides iron, therefore providing a new set of potential therapeutic targets.

MeSH terms

  • Aluminum / metabolism
  • Animals
  • Antioxidants / metabolism
  • Carrier Proteins / genetics*
  • Copper / metabolism
  • DNA-Binding Proteins / genetics*
  • Disease Models, Animal
  • Drosophila / genetics*
  • Frataxin
  • Friedreich Ataxia / genetics
  • Friedreich Ataxia / metabolism*
  • Homeostasis
  • Humans
  • Iron / metabolism*
  • Iron-Binding Proteins / genetics
  • Manganese / metabolism
  • Mitochondria / metabolism
  • Oxidative Stress
  • Transcription Factor MTF-1
  • Transcription Factors / genetics*
  • Zinc / metabolism


  • Antioxidants
  • Carrier Proteins
  • DNA-Binding Proteins
  • Iron-Binding Proteins
  • Transcription Factors
  • zinc-binding protein
  • Manganese
  • Copper
  • Aluminum
  • Iron
  • Zinc