Iron depletion in the intestines of Malvolio mutant flies does not occur in the absence of a multicopper oxidase
Iron depletion in the intestines of Malvolio mutant flies does not occur in the absence of a multicopper oxidase
复制标题
DOI：
10.1242/jeb.051664
复制
发表时间：
2011-03-01
影响因子：
2.8
通讯作者：
Missirlis, Fanis
中科院分区：
文献类型：
--
作者：
Bettedi, Lucia;Aslam, Mohamad F.;Missirlis, Fanis
Malvolio （Mvl）编码黑腹果蝇唯一的二价金属转运蛋白-1 （DMT1）同源物。果蝇转运蛋白与铁、锰和铜的细胞进口有关。事实上，在许多真核生物物种中，这种转运蛋白家族的金属特异性程度仍在研究中。在这里，我们重新审视在正常和金属补充饮食下长大的Mvl突变体的金属积累。我们发现Mvl突变果蝇缺铁，而全身铜和锰浓度保持不变。补充铁恢复了Mvl突变体的全身铁浓度，但没有补充中肠中部的铁储存，这表明Mvl除了在肠道铁吸收中起作用外，还在全身铁运输中起作用。有趣的是，饮食中硫酸铜的补充进一步加剧了铁的缺乏。我们研究了膳食铜是否通过昆虫多铜氧化酶（MCO）的功能影响铁的储存，因为已知哺乳动物MCO铜蓝蛋白可以调节肝脏中的铁储存。我们发现了一个果蝇MCO突变体，它抑制了Mvl突变体表型的某些方面，最值得注意的是Mvl、MCO3双突变体显示了正常的肠道铁储存。因此，MCO3可能编码昆虫氧化铁酶。有趣的是，MCO3突变体有轻微的铜积累，而Mvl突变体的铜积累受到抑制，这表明两个基因之间存在相互作用。
Malvolio (Mvl) encodes the sole Drosophila melanogaster homologue of divalent metal transporter-1 (DMT1). The Drosophila transporter has been implicated in iron, manganese and copper cellular import. Indeed, the extent of metal specificity for this family of transporters is still under investigation in many eukaryotic species. Here, we revisit metal accumulation in Mvl mutants raised under normal and metal-supplemented diets. We found iron deficiency in Mvl mutant flies, whereas whole body copper and manganese concentrations remained unaltered. Iron supplementation restored total body iron concentrations in Mvl mutants, but without replenishing iron stores in the middle midgut, suggesting a role for Mvl in systemic iron trafficking, in addition to a role in intestinal iron absorption. Interestingly, dietary copper sulphate supplementation further exacerbated the iron deficiency. We investigated whether dietary copper affected iron storage through the function of an insect multicopper oxidase (MCO), because the mammalian MCO ceruloplasmin is known to regulate iron storage in the liver. We identified a Drosophila MCO mutant that suppressed aspects of the Mvl mutant phenotype and most notably Mvl, MCO3 double mutants showed normal intestinal iron storage. Therefore, MCO3 may encode an insect ferroxidase. Intriguingly, MCO3 mutants had a mild accumulation of copper, which was suppressed in Mvl mutants, revealing a reciprocal genetic interaction between the two genes.