Characterization of mitochondrial ferritin in Drosophila
Characterization of mitochondrial ferritin in Drosophila
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DOI：
10.1073/pnas.0601471103
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发表时间：
2006-04-11
影响因子：
11.1
通讯作者：
Law, JH
中科院分区：
文献类型：
--
作者：
Missirlis, F;Holmberg, S;Law, JH
线粒体的功能依赖于含铁的酶和蛋白质，其成熟需要有效的铁用于铁硫簇和血红素的生物合成。关于线粒体铁稳态是如何维持的知之甚少，尽管最近在哺乳动物和植物中发现的线粒体铁蛋白揭示了这一过程中的潜在关键角色。在这里，我们表明，果蝇表达线粒体铁蛋白从一个含内含子的基因。它与小鼠和人类线粒体铁蛋白序列具有高度相似性，并且与哺乳动物一样，主要在睾丸中表达。该铁蛋白含有推定的线粒体靶向序列，并且表位标记的版本定位于转染细胞中的线粒体。线粒体铁蛋白的过度表达不能改变全身铁水平和铁结合到分泌铁蛋白。然而，铁缺乏的苍蝇的生存能力受到线粒体铁蛋白过表达的影响，这表明它可能以牺牲其他重要的细胞功能为代价螯合铁。线粒体铁蛋白在昆虫物种中的保守性强调了这种铁储存分子的重要性。
Mitochondrial function depends on iron-containing enzymes and proteins, whose maturation requires available iron for biosynthesis of iron-sulfur clusters and heme. Little is known about how mitochondrial iron homeostasis is maintained, although the recent discovery of a mitochondrial ferritin in mammals and plants has uncovered a potential key player in the process. Here, we show that Drosophila melanogaster expresses mitochondrial ferritin from an intron-containing gene. It has high similarity to the mouse and human mitochondrial ferritin sequences and, as in mammals, is expressed mainly in testis. This ferritin contains a putative mitochondrial targeting sequence and an epitope-tagged version localizes to mitochondria in transfected cells. Overexpression of mitochondrial ferritin fails to alter both total-body iron levels and iron that is bound to secretory ferritins. However, the viability of iron-deficient flies is compromised by overexpression of mitochondrial ferritin, suggesting that it may sequester iron at the expense of other important cellular functions. The conservation of mitochondrial ferritin in an insect species underscores the importance of this iron-storage molecule.