piRNA-Associated Germline Nuage Formation and Spermatogenesis Require MitoPLD Profusogenic Mitochondrial-Surface Lipid Signaling

被引:254
作者
Huang, Huiyan [1 ]
Gao, Qun [1 ]
Peng, Xiaoxue [1 ]
Choi, Seok-Yong [1 ,2 ]
Sarma, Krishna [1 ]
Ren, Hongmei [3 ]
Morris, Andrew J. [3 ]
Frohman, Michael A. [1 ]
机构
[1] SUNY Stony Brook, Dept Pharmacol, Ctr Dev Genet, Stony Brook, NY 11794 USA
[2] Chonnam Natl Univ, Sch Med, Dept Biomed Sci, Kwangju 501746, South Korea
[3] Univ Kentucky, Div Cardiovasc Med, Gill Heart Inst, Lexington, KY 40536 USA
关键词
PHOSPHOLIPASE-D; PHOSPHATIDIC-ACID; FISSION; FUSION; MEMBRANE; RECRUITMENT; DROSOPHILA; PROTEINS; DYNAMICS; PATHWAY;
D O I
10.1016/j.devcel.2011.01.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:376 / 387
页数:12
相关论文
共 33 条
[1]   Cytoplasmic Compartmentalization of the Fetal piRNA Pathway in Mice [J].
Aravin, Alexei A. ;
van der Heijden, Godfried W. ;
Castaneda, Julio ;
Vagin, Vasily V. ;
Hannon, Gregory J. ;
Bortvin, Alex .
PLOS GENETICS, 2009, 5 (12)
[2]   Dimeric PKD regulates membrane fission to form transport carriers at the TGN [J].
Bossard, Carine ;
Bresson, Damien ;
Polishchuk, Roman S. ;
Malhotra, Vivek .
JOURNAL OF CELL BIOLOGY, 2007, 179 (06) :1123-1131
[3]  
Brennecke J, 2007, CELL, V128, P1089, DOI 10.1016/j.cell.2007.01.043
[4]   Phosphatidate degradation: Phosphatidate phosphatases (lipins) and lipid phosphate phosphatases [J].
Brindley, David N. ;
Pilquil, Carlos ;
Sariahmetoglu, Meltem ;
Reue, Karen .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2009, 1791 (09) :956-961
[5]   Phospholipid signalling through phospholipase D and phosphatidic acid [J].
Cazzolli, Rosanna ;
Shemon, Anne N. ;
Fang, Michelle Q. ;
Hughes, William E. .
IUBMB LIFE, 2006, 58 (08) :457-461
[6]   Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development [J].
Chen, HC ;
Detmer, SA ;
Ewald, AJ ;
Griffin, EE ;
Fraser, SE ;
Chan, DC .
JOURNAL OF CELL BIOLOGY, 2003, 160 (02) :189-200
[7]   Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases [J].
Chen, Hsiuchen ;
Chan, David C. .
HUMAN MOLECULAR GENETICS, 2009, 18 :R169-R176
[8]   A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis [J].
Choi, Seok-Yong ;
Huang, Ping ;
Jenkins, Gary M. ;
Chan, David C. ;
Schiller, Juergen ;
Frohman, Michael A. .
NATURE CELL BIOLOGY, 2006, 8 (11) :1255-U29
[9]   Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization [J].
Colley, WC ;
Sung, TC ;
Roll, R ;
Jenco, J ;
Hammond, SM ;
Altshuller, Y ;
BarSagi, D ;
Morris, AJ ;
Frohman, MA .
CURRENT BIOLOGY, 1997, 7 (03) :191-201
[10]   Phospholipase D2 localizes to the plasma membrane and regulates angiotensin II receptor endocytosis [J].
Du, GW ;
Huang, P ;
Liang, BT ;
Frohman, MA .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (03) :1024-1030