Cells lacking pfh1, a fission yeast homolog of mammalian frataxin protein, display constitutive activation of the iron starvation response
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- dc.contributor.author Gabrielli, Natalia, 1978-ca
- dc.contributor.author Ayté del Olmo, Joséca
- dc.contributor.author Hidalgo Hernando, Elenaca
- dc.date.accessioned 2016-01-13T15:51:44Z
- dc.date.available 2016-01-13T15:51:44Z
- dc.date.issued 2012
- dc.description.abstract Friedreich ataxia is a genetic disease caused by deficiencies in frataxin. This protein has homologs not only in higher eukaryotes but also in bacteria, fungi, and plants. The function of this protein is still controversial. We have identified a frataxin homolog in fission yeast, and we have analyzed whether its depletion leads to any of the phenotypes observed in other organisms. Cells deleted in pfh1 are sensitive to growth under aerobic conditions, display increased levels of total iron, hallmarks of oxidative stress such as protein carbonylation, decreased aconitase activity, and lower levels of oxygen consumption compared with wild-type cells. This mitochondrial protein seems to be important for iron and/or reactive oxygen species homeostasis. We have analyzed the proteome of cells devoid of Pfh1, and we determined that gene products up- and down-regulated upon iron depletion in wild-type cells are constitutively misregulated in this mutant. Because of the particular signaling pathway components governing the iron starvation response in fission yeast, our experiments suggest that cells lacking Pfh1 display a decrease of cytosolic available iron that triggers activation of Grx4, the common regulator of the iron starvation gene expression program. Our Schizosaccharomyces pombe Δpfh1 strain constitutes a new and useful model system to study Friedreich ataxia.ca
- dc.description.sponsorship This work was supported in part by Spanish Ministry of Science and Innovation Grants BFU2009-06933 and BFU2012-32045, PLAN E, FEDER, by Spanish Program Consolider-Ingenio 2010 Grant CSD 2007-0020, and by Generalitat de Catalunya (Spain) Grant SGR2009-196 (to E. H.).
- dc.format.mimetype application/pdfca
- dc.identifier.citation Gabrielli N, Ayté J, Hidalgo E. Cells lacking pfh1, a fission yeast homolog of mammalian frataxin protein, display constitutive activation of the iron starvation response. J Biol Chem. 2012;287(51):43042-51. DOI: 10.1074/jbc.M112.421735ca
- dc.identifier.doi http://dx.doi.org/10.1074/jbc.M112.421735
- dc.identifier.issn 0021-9258
- dc.identifier.uri http://hdl.handle.net/10230/25570
- dc.language.iso engca
- dc.publisher American Society for Biochemistry and Molecular Biology (ASBMB)ca
- dc.relation.ispartof Journal of biological chemistry. 2012;287(51):43042-51
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-06933
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-32045
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/CSD2007-0020
- dc.rights © American Society for Biochemistry and Molecular Biology (ASBMB) /nThis research was originally published in Journal of biological chemistry. Gabrielli N, Ayté J, Hidalgo E. Cells lacking pfh1, a fission yeast homolog of mammalian frataxin protein, display constitutive activation of the iron starvation response. Journal of biological chemistry. 2012; 287(51): 43042-43051ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Schizosaccharomyces pombe -- Metabolismeca
- dc.subject.other Saccharomyces cerevisiae -- Metabolismeca
- dc.title Cells lacking pfh1, a fission yeast homolog of mammalian frataxin protein, display constitutive activation of the iron starvation responseca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca