Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, USA.
Semin Liver Dis. 2011 Aug;31(3):272-9. doi: 10.1055/s-0031-1286058. Epub 2011 Sep 7.
Systemic iron homeostasis is regulated by the interaction of the peptide hormone, hepcidin and the iron exporter, ferroportin. Mutations in FPN1, the gene that encodes ferroportin, result in iron-overload disease that shows dominant inheritance and variation in phenotype. The inheritance of ferroportin-linked disorders can be explained by the finding that ferroportin is a multimer and the product of the mutant allele participates in multimer formation. The nature of the ferroportin mutant can explain the variation in phenotype, which is due to either decreased iron export activity or decreased ability to be downregulated by hepcidin. Iron export through ferroportin is determined by the concentration of ferroportin in plasma membrane, which is the result of both synthetic and degradation events. Ferroportin degradation can occur by hepcidin-dependent and hepcidin-independent internalization. Ferroportin expression is regulated transcriptionally and posttranslationally.
系统性铁稳态由肽激素铁调素和铁输出蛋白 Ferroportin 相互作用调节。编码 Ferroportin 的 FPN1 基因突变导致铁过载疾病，呈显性遗传，表型存在差异。Ferroportin 相关疾病的遗传可通过 Ferroportin 是多聚体以及突变等位基因产物参与多聚体形成的发现来解释。Ferroportin 突变的性质可以解释表型的差异，这是由于铁输出活性降低或对铁调素的下调能力降低所致。通过 Ferroportin 的铁输出由质膜中 Ferroportin 的浓度决定，这是合成和降解事件的结果。Ferroportin 的降解可通过依赖于铁调素和不依赖于铁调素的内化发生。Ferroportin 的表达受转录和翻译后调控。
