piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling

Dev Cell. 2011 Mar 15;20(3):376-87. doi: 10.1016/j.devcel.2011.01.004.

Abstract

The mammalian Phospholipase D MitoPLD facilitates mitochondrial fusion by generating the signaling lipid phosphatidic acid (PA). The Drosophila MitoPLD homolog Zucchini (Zuc), a proposed cytoplasmic nuclease, is required for piRNA generation, a critical event in germline development. We show that Zuc localizes to mitochondria and has MitoPLD-like activity. Conversely, MitoPLD(-/-) mice exhibit the meiotic arrest, DNA damage, and male sterility characteristic of mice lacking piRNAs. The primary function of MitoPLD seems to be the generation of mitochondrial-surface PA. This PA in turn recruits the phosphatase Lipin 1, which converts PA to diacylglycerol and promotes mitochondrial fission, suggesting a mechanism for mitochondrial morphology homeostasis. MitoPLD and Lipin 1 have opposing effects on mitochondria length and on intermitochondrial cement (nuage), a structure found between aggregated mitochondria that is implicated in piRNA generation. We propose that mitochondrial-surface PA generated by MitoPLD/Zuc recruits or activates nuage components critical for piRNA production.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Embryo, Mammalian / cytology
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism*
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Germ Cells* / cytology
  • Germ Cells* / physiology
  • HeLa Cells
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Male
  • Meiosis / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • NIH 3T3 Cells
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphatidate Phosphatase
  • Phosphatidic Acids / metabolism
  • Phospholipase D / genetics
  • Phospholipase D / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Ribonucleoproteins, Small Nuclear / genetics
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Signal Transduction / physiology*
  • Spermatogenesis / physiology*

Substances

  • Drosophila Proteins
  • Isoenzymes
  • Mitochondrial Proteins
  • Nuclear Proteins
  • Phosphatidic Acids
  • RNA, Small Interfering
  • Ribonucleoproteins, Small Nuclear
  • Tdrd1 protein, mouse
  • Endoribonucleases
  • Zuc protein, Drosophila
  • Lpin1 protein, mouse
  • Phosphatidate Phosphatase
  • Phospholipase D