Frataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and lipid metabolism

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dc.contributor.authorObis Monné, Èlia
dc.contributor.authorIrazusta, Verónica Patricia
dc.contributor.authorSanchis, Daniel
dc.contributor.authorRos Salvador, Joaquim
dc.contributor.authorTamarit Sumalla, Jordi
dc.date.accessioned2016-05-09T07:57:48Z
dc.date.embargoEndDate2025-01-01
dc.date.issued2014
dc.description.abstractFriedreich ataxia (FRDA) is a hereditary disease caused by deficient frataxin expression. This mitochondrial protein has been related to iron homeostasis, energy metabolism, and oxidative stress. Patients with FRDA experience neurologic alterations and cardiomyopathy, which is the leading cause of death. The specific effects of frataxin depletion on cardiomyocytes are poorly understood because no appropriate cardiac cellular model is available to researchers. To address this research need, we present a model based on primary cultures of neonatal rat ventricular myocytes (NRVMs) and short-hairpin RNA interference. Using this approach, frataxin was reduced down to 5 to 30% of control protein levels after 7 days of transduction. At this stage the activity and amount of the iron–sulfur protein aconitase, in vitro activities of several OXPHOS components, levels of iron-regulated mRNAs, and the ATP/ADP ratio were comparable to controls. However, NRVMs exhibited markers of oxidative stress and a disorganized mitochondrial network with enlarged mitochondria. Lipids, the main energy source of heart cells, also underwent a clear metabolic change, indicated by the increased presence of lipid droplets and induction of medium-chain acyl-CoA dehydrogenase. These results indicate that mitochondria and lipid metabolism are primary targets of frataxin deficiency in NRVMs. Therefore, they contribute to the understanding of cardiac-specific mechanisms occurring in FRDA and give clues for the design of cardiac-specific treatment strategies for FRDA.ca_ES
dc.description.sponsorshipThis work was supported by grants to J.T. (La Marató deTV3 2010) and to J.R. (BFU2010-19193, CSD2007-00020 Consolider Ingenio 2010 from the Ministerio de Economia y Competitividad (Spain), and SGR2009-00196 from the Generalitat de Catalunya).ca_ES
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2014.04.016
dc.identifier.idgrec021514
dc.identifier.issn0891-5849
dc.identifier.urihttp://hdl.handle.net/10459.1/56979
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relationMICINN/PN2008-2011/BFU2010-19193
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.freeradbiomed.2014.04.016ca_ES
dc.relation.ispartofFree Radical Biology and Medicine, 2014, vol. 73, p. 21-33ca_ES
dc.rights(c) Elsevier, 2014ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.subjectFriedreichataxiaca_ES
dc.subjectMitochondriaca_ES
dc.subjectIronca_ES
dc.titleFrataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and lipid metabolismca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
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