title: The yeast metacaspase is implicated in oxidative stress response in frataxin-deficient cells.
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.
authors.affiliation: Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Université Paris-Diderot, Sorbonne Paris Cité, 15 rue Hélène Brion, 75205 Paris Cedex 13, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lefevre
authors.forename: Dominika
authors.initials: D
authors.lastname: Sliwa
authors.forename: Françoise
authors.initials: F
authors.lastname: Auchère
authors.forename: Caroline
authors.initials: C
authors.lastname: Brossas
authors.forename: Christoph
authors.initials: C
authors.lastname: Ruckenstuhl
authors.forename: Nicole
authors.initials: N
authors.lastname: Boggetto
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lesuisse
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Camadro
authors.forename: Renata
authors.initials: R
authors.lastname: Santos
mesh_terms: D020169:Caspases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D019069:Cell Respiration / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D042822:Genomic Instability / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D030781:Organisms, Genetically Modified; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015003:Yeasts / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D000096923:Frataxin
chemical_list: D020169:Caspases; D005656:Fungal Proteins; D005978:Glutathione; D006861:Hydrogen Peroxide; D033862:Iron-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D000096923:Frataxin; C456272:MCA1 protein, S cerevisiae