The classic view is that iron regulatory proteins operate at the post-transcriptional level. Iron Regulatory Protein 1 (IRP1) shifts between an apo-form that binds mRNAs and a holo-form that harbors a [4Fe4S] cluster. The latter form is not considered relevant to iron regulation, but rather thought to act as a non-essential cytosolic aconitase. Recent work in Drosophila, however, shows that holo-IRP1 can also translocate to the nucleus, where it appears to downregulate iron metabolism genes, preparing the cell for a decline in iron uptake. The shifting of IRP1 between states requires a functional mitoNEET pathway that includes a glycogen branching enzyme for the repair or disassembly of IRP1's oxidatively damaged [3Fe4S] cluster. The new findings add to the notion that glucose metabolism is modulated by iron metabolism. Furthermore, we propose that ferritin ferroxidase activity participates in the repair of the IRP1 [3Fe4S] cluster leading to the hypothesis that cytosolic ferritin directly contributes to cellular iron sensing.

中文翻译：

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蜂窝铁感测和调节：核IRP1扩展了经典范例。

经典观点是铁调节蛋白在转录后水平上起作用。铁调节蛋白1（IRP1）在结合mRNA的脱辅基形式和带有[4Fe4S]簇的完整形式之间转换。后一种形式不被认为与铁调节有关，而是被认为起非必需的胞质乌头酸酶的作用。然而，在果蝇中的最新研究表明，holo-IRP1也可以转运至细胞核，在那里似乎下调了铁代谢基因，为细胞减少铁的摄取做好了准备。IRP1在状态之间的转换需要功能性的mitoNEET途径，该途径包括糖原分支酶，用于修复或拆卸IRP1的氧化受损[3Fe4S]簇。新发现增加了葡萄糖代谢受铁代谢调节的观念。此外，