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

    Research output: Contribution to journalArticlepeer-review

    171 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)364-375
    Number of pages12
    JournalDevelopmental Cell
    Volume20
    Issue number3
    DOIs
    Publication statusPublished - Mar 15 2011

    All Science Journal Classification (ASJC) codes

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

    Fingerprint Dive into the research topics of 'MITOPLD Is a Mitochondrial Protein Essential for Nuage Formation and piRNA Biogenesis in the Mouse Germline'. Together they form a unique fingerprint.

    Cite this