MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline.

MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline.
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DOI:
10.1016/j.devcel.2011.01.005
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发表时间:
2011-03-15
期刊:
影响因子:
11.8
通讯作者:
Sasaki, Hiroyuki
Sasaki, Hiroyuki
中科院分区:
生物学1区
文献类型:
--
作者:
Watanabe, Toshiaki;Chuma, Shinichiro;Yamamoto, Yasuhiro;Kuramochi-Miyagawa, Satomi;Totoki, Yasushi;Toyoda, Atsushi;Hoki, Yuko;Fujiyama, Asao;Shibata, Tatsuhiro;Sado, Takashi;Noce, Toshiaki;Nakano, Toru;Nakatsuji, Norio;Lin, Haifan;Sasaki, Hiroyuki

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MitoPLD是磷脂酶D超家族蛋白质的一员,在不同物种中保守。西葫芦,果蝇的同源物MitoPLD,已涉及Piwi相互作用RNA(piRNA)的初级生物发生。相比之下,MitoPLD已显示水解线粒体外膜中的心磷脂以产生磷脂酸,其为信号分子。为了评估哺乳动物MitoPLD是否参与皮尔纳生物发生,我们产生了MitoPLD突变小鼠。小鼠在精子发生期间显示减数分裂停滞、逆转录转座子的去甲基化和去阻遏以及初级皮尔纳生物合成的缺陷。此外,在突变体生殖细胞中,线粒体和nuage的组分,一种参与皮尔纳生物发生/功能的核周结构,被错误定位到中心体周围的区域,表明MitoPLD可能参与线粒体和这些蛋白质的微管依赖性定位。我们的结果表明MitoPLD/Zuc在皮尔纳途径中的保守作用,并将线粒体膜代谢/信号传导与小RNA生物合成联系起来。
MitoPLD is a member of the phospholipase D superfamily proteins conserved among diverse species. Zucchini, the Drosophila homolog of MitoPLD, has been implicated in primary biogenesis of Piwi-interacting RNAs (piRNAs). By contrast, MitoPLD has been shown to hydrolyze cardiolipin in the outer membrane of mitochondria to generate phosphatidic acid, which is a signaling molecule. To assess whether the mammalian MitoPLD is involved in piRNA biogenesis, we generated MitoPLD mutant mice. The mice display meiotic arrest during spermatogenesis, demethylation and derepression of retrotransposons, and defects in primary piRNA biogenesis. Furthermore, in mutant germ cells, mitochondria and the components of the nuage, a perinuclear structure involved in piRNA biogenesis/function, are mislocalized to regions around the centrosome, suggesting that MitoPLD may be involved in microtubule-dependent localization of mitochondria and these proteins. Our results indicate a conserved role for MitoPLD/Zuc in the piRNA pathway and link mitochondrial membrane metabolism/signaling to small RNA biogenesis.
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