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.
|Number of pages||12|
|State||Published - Mar 15 2011|
Bibliographical noteFunding Information:
We thank Drs. S. Chuma (Kyoto U.), R. Jessberger (Dresden U. Tech.), A. Vasileva (Mt. Sinai), S. K-Miyagawa and T. Nakano (Osaka U.), and C. Chen and T. Pawson (Samuel Lunenfeld Res. Inst.) for the kind gifts of piRNA pathway expression plasmids, Dr. A. Newton for the DAG sensor, B. Cyge for advice, Y. Altshuller for generating innumerable plasmid constructs, and many colleagues for critical manuscript feedback. Supported by NIH (GM071520, GM084251 to M.A.F.; GM50388, P20RR021954 to A.J.M.) and fellowships from NIH (T32-DK07521) and AHA to Q.G. and H.R.
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology (all)
- Developmental Biology
- Cell Biology