| First Author | Rishi G | Year | 2020 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1866 |
| Issue | 10 | Pages | 165882 |
| PubMed ID | 32565019 | Mgi Jnum | J:299445 |
| Mgi Id | MGI:6490801 | Doi | 10.1016/j.bbadis.2020.165882 |
| Citation | Rishi G, et al. (2020) Hepatocyte-specific deletion of peroxisomal protein PEX13 results in disrupted iron homeostasis. Biochim Biophys Acta Mol Basis Dis 1866(10):165882 |
| abstractText | 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. |
