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dc.contributor.authorRishi, Gautam
dc.contributor.authorBhatia, Maneet
dc.contributor.authorSecondes, Eriza S
dc.contributor.authorMelino, Michelle
dc.contributor.authorCrane, Denis
dc.contributor.authorSubramaniam, V Nathan
dc.date.accessioned2021-02-15T03:54:20Z
dc.date.available2021-02-15T03:54:20Z
dc.date.issued2020
dc.identifier.issn0925-4439
dc.identifier.doi10.1016/j.bbadis.2020.165882
dc.identifier.urihttp://hdl.handle.net/10072/402144
dc.description.abstractPeroxisomes are organelles, abundant in the liver, involved in a variety of cellular functions, including fatty acid metabolism, plasmalogen synthesis and metabolism of reactive oxygen species. Several inherited disorders are associated with peroxisomal dysfunction; increasingly many are associated with hepatic pathologies. The liver plays a principal role in regulation of iron metabolism. In this study we examined the possibility of a relationship between iron homeostasis and peroxisomal integrity. We examined the effect of deleting Pex13 in mouse liver on systemic iron homeostasis. We also used siRNA-mediated knock-down of PEX13 in a human hepatoma cell line (HepG2/C3A) to elucidate the mechanisms of PEX13-mediated regulation of hepcidin. We demonstrate that transgenic mice lacking hepatocyte Pex13 have defects in systemic iron homeostasis. The ablation of Pex13 expression in hepatocytes leads to a significant reduction in hepatic hepcidin levels. Our results also demonstrate that a deficiency of PEX13 gene expression in HepG2/C3A cells leads to decreased hepcidin expression, which is mediated through an increase in the signalling protein SMAD7, and endoplasmic reticulum (ER) stress. This study identifies a novel role for a protein involved in maintaining peroxisomal integrity and function in iron homeostasis. Loss of Pex13, a protein important for peroxisomal function, in hepatocytes leads to a significant increase in ER stress, which if unresolved, can affect liver function. The results from this study have implications for the management of patients with peroxisomal disorders and the liver-related complications they may develop.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherElsevier
dc.relation.ispartofpagefrom165882
dc.relation.ispartofissue10
dc.relation.ispartofjournalBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
dc.relation.ispartofvolume1866
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3205
dc.subject.fieldofresearchcode3202
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsBiophysics
dc.subject.keywordsMolecular Biology
dc.titleHepatocyte-specific deletion of peroxisomal protein PEX13 results in disrupted iron homeostasis
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationRishi, G; Bhatia, M; Secondes, ES; Melino, M; Crane, D; Subramaniam, VN, Hepatocyte-specific deletion of peroxisomal protein PEX13 results in disrupted iron homeostasis, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2020, 1866 (10), pp. 165882
dcterms.dateAccepted2020-06-16
dc.date.updated2021-02-15T03:53:00Z
gro.hasfulltextNo Full Text
gro.griffith.authorCrane, Denis I.


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