MITOPLD Is a Mitochondrial Protein Essential for Nuage Formation and piRNA Biogenesis in the Mouse Germline

Toshiaki Watanabe, Shinichiro Chuma, Yasuhiro Yamamoto, Satomi Kuramochi-Miyagawa, Yasushi Totoki, Atsushi Toyoda, Yuko Hoki, Asao Fujiyama, Tatsuhiro Shibata, Takashi Sado, Toshiaki Noce, Toru Nakano, Norio Nakatsuji, Haifan Lin, Hiroyuki Sasaki

    研究成果: Contribution to journalArticle査読

    173 被引用数 (Scopus)


    MITOPLD is a member of the phospholipase D superfamily proteins conserved among diverse species. Zucchini (Zuc), 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.

    ジャーナルDevelopmental Cell
    出版ステータス出版済み - 3 15 2011

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Developmental Biology
    • Cell Biology

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