Functional characterization of drim2, the Drosophila melanogaster homolog of the yeast mitochondrial deoxynucleotide transporter.
Functional characterization of drim2, the Drosophila melanogaster homolog of the yeast mitochondrial deoxynucleotide transporter.
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DOI：
10.1074/jbc.m113.543926
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发表时间：
2014-03-14
期刊：
影响因子：
--
通讯作者：
Costa R
中科院分区：
文献类型：
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作者：
Da-Rè C;Franzolin E;Biscontin A;Piazzesi A;Pacchioni B;Gagliani MC;Mazzotta G;Tacchetti C;Zordan MA;Zeviani M;Bernardi P;Bianchi V;De Pittà C;Costa R
背景：载体介导的胞质脱氧核苷酸内流是线粒体DNA合成前体的主要来源。结果：dRIM2是维持果蝇线粒体正常脱氧核苷酸库所必需的，其敲除在幼虫期具有致死性。结论：dRIM2是一种脱氧核苷酸载体，对维持线粒体功能至关重要。意义：我们的数据提供了第一个RIM2缺乏症的动物模型。CG18317基因（drim2）是与酿酒酵母（Saccharomyces cerevisiae） Rim2基因同源的果蝇黑胃基因（Drosophila melanogaster），其编码嘧啶（脱氧）核苷酸载体。在这里，我们测试了drim2基因是否也编码果蝇的脱氧核苷酸转运体。该蛋白定位于线粒体。果蝇S2R+细胞对drim2表达沉默后，线粒体中嘌呤和嘧啶dNTPs池均显著减少，而细胞质池未受影响。在体内，drim2纯合子敲除在幼虫期是致命的，在此之前会出现以下情况：(i)运动行为受损；（ii）氧气消耗速率降低，（iii） mtDNA耗竭。我们得出结论，果蝇线粒体载体dRIM2运输所有DNA前体，对维持线粒体功能至关重要。
Background: Carrier-mediated influx of cytosolic deoxynucleotides is a major source of precursors for mitochondrial DNA synthesis. Results: dRIM2 is required to maintain normal deoxynucleotide pools in Drosophila mitochondria, and its knock-out is lethal at the larval stage. Conclusion: dRIM2 is a deoxynucleotide carrier and is essential to maintain mitochondrial function. Significance: Our data provide the first animal model of RIM2 deficiency. The CG18317 gene (drim2) is the Drosophila melanogaster homolog of the Saccharomyces cerevisiae Rim2 gene, which encodes a pyrimidine (deoxy)nucleotide carrier. Here, we tested if the drim2 gene also encodes for a deoxynucleotide transporter in the fruit fly. The protein was localized to mitochondria. Drosophila S2R+ cells, silenced for drim2 expression, contained markedly reduced pools of both purine and pyrimidine dNTPs in mitochondria, whereas cytosolic pools were unaffected. In vivo drim2 homozygous knock-out was lethal at the larval stage, preceded by the following: (i) impaired locomotor behavior; (ii) decreased rates of oxygen consumption, and (iii) depletion of mtDNA. We conclude that the Drosophila mitochondrial carrier dRIM2 transports all DNA precursors and is essential to maintain mitochondrial function.