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PMID:21397847

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Citation

Watanabe, T, Chuma, S, Yamamoto, Y, Kuramochi-Miyagawa, S, Totoki, Y, Toyoda, A, Hoki, Y, Fujiyama, A, Shibata, T, Sado, T, Noce, T, Nakano, T, Nakatsuji, N, Lin, H and Sasaki, H (2011) MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline. Dev. Cell 20:364-75

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.

Links

PubMed PMC3062204 Online version:10.1016/j.devcel.2011.01.005

Keywords

Animals; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Endoribonucleases/genetics; Endoribonucleases/metabolism; Germ Cells/cytology; Germ Cells/physiology; Humans; Isoenzymes/genetics; Isoenzymes/metabolism; Male; Meiosis/physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Phospholipase D/genetics; Phospholipase D/metabolism; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; Retroelements; Signal Transduction/physiology; Spermatogenesis/physiology; Testis/cytology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PLD6

involved_in

GO:0007286: spermatid development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLD6

located_in

GO:0005741: mitochondrial outer membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PLD6

involved_in

GO:0051321: meiotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLD6

involved_in

GO:0043046: DNA methylation involved in gamete generation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLD6

involved_in

GO:0034587: piRNA metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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