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.

过氧化物酶体是在肝脏中丰富的细胞器，参与多种细胞功能，包括脂肪酸代谢，缩醛磷脂合成和活性氧代谢。几种遗传性疾病与过氧化物酶体功能障碍有关。越来越多的人与肝脏疾病有关。肝脏在铁代谢的调节中起主要作用。在这项研究中，我们研究了铁稳态与过氧化物酶体完整性之间关系的可能性。

我们检查了删除小鼠肝脏中Pex13对全身铁稳态的影响。我们还使用siRNA介导的人类肝癌细胞系（HepG2 / C3A）中PEX13的敲低来阐明PEX13介导的铁调素调节的机制。

我们证明缺乏肝细胞Pex13的转基因小鼠在全身铁稳态中存在缺陷。肝细胞中Pex13表达的消融导致肝铁调素水平显着降低。我们的研究结果还表明，HepG2 / C3A细胞中PEX13基因表达的缺失会导致铁调素表达降低，这是通过信号蛋白SMAD7和内质网（ER）应激的增加介导的。

这项研究确定了一种蛋白质的新作用，参与维持铁稳态中的过氧化物酶体完整性和功能。Pex13（一种对过氧化物酶体功能至关重要的蛋白质）在肝细胞中的丢失会导致ER压力显着增加，如果无法解决，则会影响肝功能。这项研究的结果对过氧化物酶体紊乱患者及其可能发生的与肝有关的并发症的治疗具有重要意义。