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.
Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Caspases / genetics*
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Caspases / metabolism
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Caspases / physiology
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Cell Respiration / genetics
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Dose-Response Relationship, Drug
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Frataxin
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Fungal Proteins / genetics
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Fungal Proteins / physiology
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Genomic Instability / genetics
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Glutathione / metabolism
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Humans
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Hydrogen Peroxide / pharmacology
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Iron-Binding Proteins / genetics*
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Iron-Binding Proteins / physiology
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondria / physiology
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Organisms, Genetically Modified
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Oxidation-Reduction
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Oxidative Stress / drug effects
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Oxidative Stress / genetics*
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Oxidative Stress / physiology
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Saccharomyces cerevisiae / enzymology
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Saccharomyces cerevisiae Proteins / physiology
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Yeasts / enzymology
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Yeasts / genetics
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Yeasts / growth & development
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Yeasts / metabolism
Substances
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Fungal Proteins
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Iron-Binding Proteins
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Saccharomyces cerevisiae Proteins
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Hydrogen Peroxide
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Caspases
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MCA1 protein, S cerevisiae
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Glutathione