9lky

Structural highlights

Function

PLD6_HUMAN Presents phospholipase and nuclease activities, depending on the different physiological conditions (PubMed:17028579, PubMed:21397847, PubMed:28063496). Interaction with Mitoguardin (MIGA1 or MIGA2) affects the dimer conformation, facilitating the lipase activity over the nuclease activity (PubMed:26711011). Plays a key role in mitochondrial fusion and fission via its phospholipase activity (PubMed:17028579, PubMed:24599962, PubMed:26678338). In its phospholipase role, it uses the mitochondrial lipid cardiolipin as substrate to generate phosphatidate (PA or 1,2-diacyl-sn-glycero-3-phosphate), a second messenger signaling lipid (PubMed:17028579, PubMed:26711011). Production of PA facilitates Mitofusin-mediated fusion, whereas the cleavage of PA by the Lipin family of phosphatases produces diacylgycerol (DAG) which promotes mitochondrial fission (PubMed:24599962). Both Lipin and DAG regulate mitochondrial dynamics and membrane fusion/fission, important processes for adapting mitochondrial metabolism to changes in cell physiology. Mitochondrial fusion enables cells to cope with the increased nucleotide demand during DNA synthesis (PubMed:26678338). Mitochondrial function and dynamics are closely associated with biological processes such as cell growth, proliferation, and differentiation (PubMed:21397848). Mediator of MYC activity, promotes mitochondrial fusion and activates AMPK which in turn inhibits YAP/TAZ, thereby inducing cell growth and proliferation (PubMed:26678338). The endonuclease activity plays a critical role in PIWI-interacting RNA (piRNA) biogenesis during spermatogenesis (PubMed:21397847, PubMed:21397848). Implicated in spermatogenesis and sperm fertility in testicular germ cells, its single strand-specific nuclease activity is critical for the biogenesis/maturation of PIWI-interacting RNA (piRNA). MOV10L1 selectively binds to piRNA precursors and funnels them to the endonuclease that catalyzes the first cleavage step of piRNA processing to generate piRNA intermediate fragments that are subsequently loaded to Piwi proteins. Cleaves either DNA or RNA substrates with similar affinity, producing a 5' phosphate end, in this way it participates in the processing of primary piRNA transcripts. piRNAs provide essential protection against the activity of mobile genetic elements. piRNA-mediated transposon silencing is thus critical for maintaining genome stability, in particular in germline cells when transposons are mobilized as a consequence of wide-spread genomic demethylation (By similarity). PA may act as signaling molecule in the recognition/transport of the precursor RNAs of primary piRNAs (PubMed:21397847). Interacts with tesmin in testes, suggesting a role in spermatogenesis via association with its interacting partner (By similarity).[UniProtKB:Q5SWZ9]^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Choi SY, Huang P, Jenkins GM, Chan DC, Schiller J, Frohman MA. A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis. Nat Cell Biol. 2006 Nov;8(11):1255-62. PMID:17028579 doi:10.1038/ncb1487
2. ↑ 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, Sasaki H. MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline. Dev Cell. 2011 Mar 15;20(3):364-75. doi: 10.1016/j.devcel.2011.01.005. PMID:21397847 doi:http://dx.doi.org/10.1016/j.devcel.2011.01.005
3. ↑ Huang H, Gao Q, Peng X, Choi SY, Sarma K, Ren H, Morris AJ, Frohman MA. 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. PMID:21397848 doi:10.1016/j.devcel.2011.01.004
4. ↑ Baba T, Kashiwagi Y, Arimitsu N, Kogure T, Edo A, Maruyama T, Nakao K, Nakanishi H, Kinoshita M, Frohman MA, Yamamoto A, Tani K. Phosphatidic acid (PA)-preferring phospholipase A1 regulates mitochondrial dynamics. J Biol Chem. 2014 Apr 18;289(16):11497-511. doi: 10.1074/jbc.M113.531921. Epub, 2014 Mar 5. PMID:24599962 doi:http://dx.doi.org/10.1074/jbc.M113.531921
5. ↑ von Eyss B, Jaenicke LA, Kortlever RM, Royla N, Wiese KE, Letschert S, McDuffus LA, Sauer M, Rosenwald A, Evan GI, Kempa S, Eilers M. A MYC-Driven Change in Mitochondrial Dynamics Limits YAP/TAZ Function in Mammary Epithelial Cells and Breast Cancer. Cancer Cell. 2015 Dec 14;28(6):743-757. PMID:26678338 doi:10.1016/j.ccell.2015.10.013
6. ↑ Zhang Y, Liu X, Bai J, Tian X, Zhao X, Liu W, Duan X, Shang W, Fan HY, Tong C. Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis. Mol Cell. 2016 Jan 7;61(1):111-24. PMID:26711011 doi:10.1016/j.molcel.2015.11.017
7. ↑ Philip F, Ha EE, Seeliger MA, Frohman MA. Measuring Phospholipase D Enzymatic Activity Through Biochemical and Imaging Methods. Methods Enzymol. 2017;583:309-325. PMID:28063496 doi:10.1016/bs.mie.2016.09.041