Iron is biologically essential and participates in a wide variety of metabolic processes including oxygen transport, oxidative metabolism and cellular proliferation. However, iron is also potentially toxic and abnormal iron levels have been associated with several disorders, including iron deficiency anemia, porphyrias and neurodegenerative disorders such as multiple sclerosis (MS). Iron level must therefore be tightly controlled to prevent both deficiency and overload. A new study identifies Ecotropic viral integration site 5 (Evi5) as a new regulator of vesicular iron transport in Drosophila. Evi5 was identified via an RNAi screen in the Drosophila prothoracic gland (PG), a tissue that requires abundant amounts of iron to produce the hormone ecdysone. PG-specific depletion of Evi5 led to developmental delays, as well as reduced cellular iron levels, changes in vesicle morphology and abundance, impaired trafficking of transferrin-1, which disrupted heme and ecdysone synthesis. These findings could explain why Evi5 has been identified as a high-risk locus for MS, a disease that presents with excess iron in the central nervous system.

Original reference: Soltani, S. et al. Nat. Commun. 15, 4045 (2024)

铁在生物学上是必需的，参与多种代谢过程，包括氧运输、氧化代谢和细胞增殖。然而，铁也具有潜在的毒性，铁含量异常与多种疾病有关，包括缺铁性贫血、卟啉症和多发性硬化症 (MS) 等神经退行性疾病。因此，必须严格控制铁含量，以防止缺乏和过量。一项新研究确定了生态性病毒整合位点 5 (Evi5) 是果蝇囊泡铁转运的新调节因子。 Evi5是通过果蝇前胸腺（PG）中的RNAi筛选鉴定出来的，该组织需要大量的铁来产生激素蜕皮激素。 Evi5的 PG 特异性缺失会导致发育迟缓、细胞铁水平降低、囊泡形态和丰度变化、转铁蛋白-1 运输受损，从而扰乱血红素和蜕皮激素合成。这些发现可以解释为什么Evi5被确定为多发性硬化症的高风险位点，多发性硬化症是一种中枢神经系统铁过多的疾病。

原始参考文献： Soltani, S. 等人。纳特。交流。 15 , 4045 (2024)