TY - JOUR
T1 - MITOPLD Is a Mitochondrial Protein Essential for Nuage Formation and piRNA Biogenesis in the Mouse Germline
AU - Watanabe, Toshiaki
AU - Chuma, Shinichiro
AU - Yamamoto, Yasuhiro
AU - Kuramochi-Miyagawa, Satomi
AU - Totoki, Yasushi
AU - Toyoda, Atsushi
AU - Hoki, Yuko
AU - Fujiyama, Asao
AU - Shibata, Tatsuhiro
AU - Sado, Takashi
AU - Noce, Toshiaki
AU - Nakano, Toru
AU - Nakatsuji, Norio
AU - Lin, Haifan
AU - Sasaki, Hiroyuki
N1 - Funding Information:
We thank J. Martinez and D. Pezic for the MIWI2 antibody; T. Tanaka for information about the DDX6 antibody; S.-Y. Choi and V. Gangaraju for advice of MITOPLD protein purification; A. Aravin and G.J. Hannon for small RNA sequence information; K. Ichiyanagi, H. Furuumi, Y. Tsutsui, R. Fujita, and T. Horiike for scientific and technical advice; N. Iida and H. Horiike for technical assistance. The small RNA sequences are registered in NCBI Gene Expression Omnibus with the accession number GSE20327. T.W. is a JSPS Postdoctoral Fellow for Research Abroad. This work was supported in part by Grants-in-Aid for Scientific Research on Priority Area from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to H.S. and by NIH R01HD42012 to H.L.
PY - 2011/3/15
Y1 - 2011/3/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.devcel.2011.01.005
DO - 10.1016/j.devcel.2011.01.005
M3 - Article
C2 - 21397847
AN - SCOPUS:79952525007
SN - 1534-5807
VL - 20
SP - 364
EP - 375
JO - Developmental Cell
JF - Developmental Cell
IS - 3
ER -