The yeast metacaspase is implicated in oxidative stress response in frataxin-deficient cells

FEBS Lett. 2012 Jan 20;586(2):143-8. doi: 10.1016/j.febslet.2011.12.002. Epub 2011 Dec 7.

Abstract

Friedreich ataxia is the most common recessive neurodegenerative disease and is caused by reduced expression of mitochondrial frataxin. Frataxin depletion causes impairment in iron-sulfur cluster and heme biosynthesis, disruption of iron homeostasis and hypersensitivity to oxidants. Currently no pharmacological treatment blocks disease progression, although antioxidant therapies proved to benefit patients. We show that sensitivity of yeast frataxin-deficient cells to hydrogen peroxide is partially mediated by the metacaspase. Metacaspase deletion in frataxin-deficient cells results in recovery of antioxidant capacity and heme synthesis. In addition, our results suggest that metacaspase is associated with mitochondrial respiration, intracellular redox control and genomic stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspases / genetics*
  • Caspases / metabolism
  • Caspases / physiology
  • Cell Respiration / genetics
  • Dose-Response Relationship, Drug
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology
  • Genomic Instability / genetics
  • Glutathione / metabolism
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Iron-Binding Proteins / genetics*
  • Iron-Binding Proteins / physiology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Organisms, Genetically Modified
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics*
  • Oxidative Stress / physiology
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology
  • Yeasts / enzymology
  • Yeasts / genetics
  • Yeasts / growth & development
  • Yeasts / metabolism

Substances

  • Fungal Proteins
  • Iron-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • frataxin
  • Hydrogen Peroxide
  • Caspases
  • MCA1 protein, S cerevisiae
  • Glutathione