dc.contributor.author | Rishi, Gautam | |
dc.contributor.author | Bhatia, Maneet | |
dc.contributor.author | Secondes, Eriza S | |
dc.contributor.author | Melino, Michelle | |
dc.contributor.author | Crane, Denis | |
dc.contributor.author | Subramaniam, V Nathan | |
dc.date.accessioned | 2021-02-15T03:54:20Z | |
dc.date.available | 2021-02-15T03:54:20Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 0925-4439 | |
dc.identifier.doi | 10.1016/j.bbadis.2020.165882 | |
dc.identifier.uri | http://hdl.handle.net/10072/402144 | |
dc.description.abstract | Peroxisomes 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.peerreviewed | Yes | |
dc.language | English | |
dc.publisher | Elsevier | |
dc.relation.ispartofpagefrom | 165882 | |
dc.relation.ispartofissue | 10 | |
dc.relation.ispartofjournal | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | |
dc.relation.ispartofvolume | 1866 | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearch | Medical biochemistry and metabolomics | |
dc.subject.fieldofresearch | Clinical sciences | |
dc.subject.fieldofresearchcode | 3101 | |
dc.subject.fieldofresearchcode | 3205 | |
dc.subject.fieldofresearchcode | 3202 | |
dc.subject.keywords | Science & Technology | |
dc.subject.keywords | Life Sciences & Biomedicine | |
dc.subject.keywords | Biophysics | |
dc.subject.keywords | Molecular Biology | |
dc.title | Hepatocyte-specific deletion of peroxisomal protein PEX13 results in disrupted iron homeostasis | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Rishi, 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.dateAccepted | 2020-06-16 | |
dc.date.updated | 2021-02-15T03:53:00Z | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Crane, Denis I. | |