Ferritin is the key to dietary iron absorption and tissue iron detoxification in Drosophila melanogaster
Ferritin is the key to dietary iron absorption and tissue iron detoxification in Drosophila melanogaster
复制标题
铁蛋白是果蝇膳食铁吸收和组织铁解毒的关键
DOI：
10.1096/fj.12-213595
复制
发表时间：
2013-01-01
期刊：
影响因子：
4.8
通讯作者：
Zhou, Bing
中科院分区：
文献类型：
--
作者：
Tang, Xiaona;Zhou, Bing
哺乳动物的铁蛋白主要存在于细胞质中，少量存在于血浆中。在包括黑腹果蝇在内的大多数昆虫中，铁蛋白属于分泌型。无论是在昆虫还是哺乳动物中，分泌型铁蛋白在铁稳态中的功能作用仍知之甚少。在此，我们利用果蝇来剖析铁蛋白在昆虫铁代谢中的作用。中肠特异性敲低铁蛋白会导致肠道内铁积累，但全身铁缺乏（为对照组的37%），同时发育迟缓且存活率降低（存活率为3%），而通过饮食补充铁可挽救这种情况（存活率达50%），缺铁则会加剧这种状况（存活率为0%）。这些结果表明，铁蛋白在将铁从肠细胞跨基底外侧膜转运出去的过程中发挥着关键作用。在中肠，尤其是铁细胞区域表达野生型铁蛋白，能够显著挽救铁蛋白缺失突变体（一龄幼虫可存活至成虫早期），这表明铁缺乏是铁蛋白缺陷型果蝇过早死亡的主要原因。在许多非肠道组织中，组织特异性敲低铁蛋白也会导致局部铁积累（增加100%），并造成严重的组织损伤，细胞缺失就是证明。总体而言，我们的研究表明，果蝇铁蛋白对铁稳态的两个关键方面至关重要：膳食铁吸收和组织铁解毒。——唐X，周B。铁蛋白是黑腹果蝇膳食铁吸收和组织铁解毒的关键。《美国实验生物学会联合会杂志》27卷，288 - 298页（2013年）。www.fasebj.org
Mammalian ferritin is predominantly in the cytosol, with a minor portion found in plasma. In most insects, including Drosophila melanogaster, ferritin belongs to the secretory type. The functional role of secretory ferritin in iron homeostasis remains poorly understood in insects as well as in mammalians. Here we used Drosophila to dissect the involvement of ferritin in insect iron metabolism. Midgut‐specific knockdown of ferritin resulted in iron accumulation in the gut but systemic iron deficiency (37% control), accompanied by retarded development and reduced survival (3% survival), and was rescued by dietary iron supplementation (50% survival) or exacerbated by iron depletion (0% survival). These results suggest an essential role of ferritin in removing iron from enterocytes across the basolateral membrane. Expression of wild‐type ferritin in the midgut, especially in the iron cell region, could significantly rescue ferritin‐null mutants (first‐instar larvae rescued up to early adults), indicating iron deficiency as the major cause of early death for ferritin flies. In many nonintestinal tissues, tissue‐specific ferritin knockdown also caused local iron accumulation (100% increase) and resulted in severe tissue damage, as evidenced by cell loss. Overall, our study demonstrated Drosophila ferritin is essential to two key aspects of iron homeostasis: dietary iron absorption and tissue iron detoxification.—Tang, X., Zhou, B. Ferritin is the key to dietary iron absorption and tissue iron detoxification in Drosophila melanogaster. FASEB J. 27, 288–298 (2013). www.fasebj.org