Affinage

PLD6

Mitochondrial cardiolipin hydrolase · UniProt Q8N2A8

Length
252 aa
Mass
28.3 kDa
Annotated
2026-06-10
73 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLD6 (Zucchini/MitoPLD) is a phospholipase D superfamily protein at the mitochondrial outer membrane that bridges two distinct biological programs: small-RNA biogenesis in the germline and mitochondrial membrane dynamics (PMID:21397847, PMID:21397848). As an enzyme, it possesses dual catalytic outputs documented by orthogonal structural and biochemical work: it acts as a single-strand-specific endoribonuclease that cleaves RNA to generate the 5'-monophosphorylated ends that define mature primary piRNAs, a function established by crystal structures of the dimeric Drosophila and mouse proteins together with active-site mutagenesis and in vivo piRNA/transposon phenotypes (PMID:23064230, PMID:23064227), and the human orthologue retains this endonuclease activity in vitro (PMID:28063496). In parallel, PLD6 hydrolyzes cardiolipin to produce the signaling lipid phosphatidic acid (PA) on the mitochondrial surface (PMID:21397848, PMID:37277481). In germ cells, PLD6 is required for primary piRNA biogenesis, retrotransposon silencing, and meiotic progression, and its loss causes male sterility; it operates within the perinuclear nuage in physical and genetic association with PIWI-pathway factors including Aubergine, the helicase Armitage/MOV10L1, and the Papi/ZUC-processor machinery (PMID:17543859, PMID:21397847, PMID:33635934, PMID:29489748), with PLD6 generating 5' ends in mice and trimming 3' ends within a sequence-defined cleavage window across species (PMID:35669519, PMID:29489748). PLD6-derived PA constitutes a membrane-remodeling signal: it is counterbalanced by Lipin 1 to control mitochondrial fission and nuage architecture (PMID:21397848), and recruits effectors such as NME3 — which binds PA-induced packing defects via an amphipathic helix to drive selective mitochondrial tethering and fusion (PMID:37584589) — as well as the glycerol-kinase-like proteins GYKL1/GK2 to promote mitochondrial clustering during spermiogenesis (PMID:28852571). The same PA output mediates fusion of LDLR-positive endocytic vesicles with mitochondria for cholesterol delivery to steroidogenesis (PMID:37277481) and participates in PINK1/Parkin-dependent mitophagy (PMID:41640016). PLD6 protein levels are controlled by proteasomal turnover through a TOM20–FEM1B–CRL2 axis that recognizes PLD6 at the mitochondrial import receptor (PMID:40263465). PLD6 retrotransposon silencing is predominantly posttranscriptional, via RNA degradation rather than DNA methylation (PMID:28749988). In cancer cells, PLD6 modulates mitochondrial metabolism to influence YAP/TAZ and Wnt/β-catenin signaling (PMID:26678338, PMID:40259095).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2007 High

    Established Zucchini/PLD6 as a nuclease-domain protein genetically required for the piRNA pathway, placing it physically in the nuage with PIWI proteins before its enzymatic activity was defined.

    Evidence Co-IP with Aubergine, nuage immunofluorescence, and loss-of-function transposon/rasiRNA phenotypes in Drosophila

    PMID:17543859

    Open questions at the time
    • Direct enzymatic activity not yet demonstrated
    • No structural basis for substrate specificity
    • Mammalian relevance untested at this stage
  2. 2011 High

    Defined the mammalian protein as a mitochondrial outer-membrane enzyme whose loss phenocopies piRNA mutants and revealed its phosphatidic-acid-generating activity, connecting mitochondrial lipid signaling to piRNA biogenesis and mitochondrial morphology.

    Evidence Pld6 knockout mice with meiotic/transposon/piRNA phenotypes, lipid biochemistry of PA generation, and Lipin1 epistasis with mitochondrial morphology readouts

    PMID:21397847 PMID:21397848

    Open questions at the time
    • Whether nuclease or phospholipase activity drives piRNA biogenesis unresolved
    • Direct in vitro enzymatic demonstration not yet provided
    • PA effector proteins not identified
  3. 2012 High

    Resolved the long-standing PLD-vs-nuclease question by showing the protein is a dimeric single-strand-specific endoribonuclease generating 5'-monophosphate piRNA ends, providing a structural and catalytic mechanism for primary piRNA maturation.

    Evidence Crystal structures (1.75 Å) of Drosophila and mouse Zuc, in vitro ssRNA cleavage assays, active-site mutagenesis, and in vivo piRNA/transposon validation

    PMID:23064227 PMID:23064230

    Open questions at the time
    • How the two enzymatic activities are partitioned in vivo unclear
    • Substrate selection upstream of cleavage not defined
    • No human structural data
  4. 2017 Medium

    Mapped the PA-signaling output to specific effectors and tissue contexts, showing PLD6 cooperates with glycerol-kinase-like proteins for mitochondrial clustering in spermiogenesis and that female germline piRNA biogenesis is only partially PLD6-dependent.

    Evidence Co-IP and KO mice for Gykl1/Gk2 with PA assays and mitochondrial sheath morphology; comparative small-RNA sequencing in Pld6/Mili oocyte knockouts; Bombyx domain-mapping of mitochondrial targeting

    PMID:28115634 PMID:28852571 PMID:28942151

    Open questions at the time
    • Identity of compensating 5'-end enzyme in oocytes unknown
    • Mechanism coupling PA to clustering not fully reconstituted
    • Single-lab observations
  5. 2018 High

    Revealed species-specific use of Zuc within piRNA biogenesis, demonstrating in Bombyx that Zuc trims 3' ends of intermediates accumulated in the Papi complex, establishing a hierarchical biogenesis model distinct from the 5'-end role.

    Evidence Bombyx Zuc knockout, in vitro processing with recombinant Zuc, and 5'/3'-end small-RNA sequencing with Papi complex characterization

    PMID:29489748

    Open questions at the time
    • Whether mammalian PLD6 performs analogous 3' trimming in vivo not settled
    • Determinants of 5' vs 3' specificity unclear
  6. 2021 High

    Clarified the silencing mechanism and an essential biogenesis partner, showing PLD6-mediated transposon repression is primarily posttranscriptional RNA degradation and that the MOV10L1–PLD6 interaction is required for piRNA 5'-end generation.

    Evidence Pld6/Dnmt3l double-KO epistasis with methylation/RNA profiling; Mov10l1 V229E point mutant with Co-IP and small-RNA sequencing

    PMID:28749988 PMID:33635934

    Open questions at the time
    • Structural basis of MOV10L1–PLD6 contact unknown
    • How RNA degradation is mechanistically executed not detailed
  7. 2023 High

    Generalized the PA-effector model beyond germline by identifying NME3 as a PA-binding tethering factor for selective mitochondrial fusion and showing PLD6 cardiolipin hydrolysis drives endocytic-vesicle–mitochondria fusion for cholesterol delivery.

    Evidence NME3 lipid-binding reconstitution, amphipathic-helix mutagenesis, KO imaging; genome-wide shRNA screen, CISD2–LDLR Co-IP, PA biochemistry, and PLD6 KO vesicle/cholesterol trafficking assays

    PMID:37277481 PMID:37584589

    Open questions at the time
    • How PLD6 activity is spatially restricted to fusion sites unclear
    • Relationship between cardiolipin and PA substrate pools not resolved
  8. 2025 High

    Defined post-translational control of PLD6 abundance, showing a TOM20-recruited FEM1B/CRL2 ligase governs proteasomal turnover of PLD6 to constrain mitochondrial elongation/clustering.

    Evidence Proteomics, Co-IP of FEM1B–PLD6 and FEM1B–TOM20, structural analysis, and FEM1B KO mitochondrial morphology readouts

    PMID:40263465

    Open questions at the time
    • Signals triggering PLD6 degradation not defined
    • Whether turnover regulates nuclease vs lipase functions distinctly unknown
  9. 2025 Medium

    Extended PLD6 into oncogenic signaling, linking its control of mitochondrial metabolism to acetyl-CoA-dependent β-catenin acetylation and Wnt activation, and to MYC-driven AMPK/YAP-TAZ suppression.

    Evidence PLD6 KD/KO in CRC cells with respiration assays, metabolomics, β-catenin acetylation assays and tumor models; MYC epistasis with AMPK/YAP-TAZ readouts in mammary models

    PMID:26678338 PMID:40259095

    Open questions at the time
    • Whether these effects require PLD6 catalytic activity unclear
    • Single-lab contexts
    • Direct PLD6 enzymatic link to metabolic output not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PLD6's two catalytic activities (RNA cleavage vs cardiolipin hydrolysis) and its discrepant subcellular localizations (mitochondria vs Golgi) are coordinated within a single cell remains unresolved.
  • No structural model explaining how one enzyme cleaves both RNA and lipid
  • Endogenous Golgi/surface localization not mechanistically reconciled with mitochondrial function
  • Human in vivo function inferred largely from model organisms

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0003723 RNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005739 mitochondrion 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1474165 Reproduction 2 R-HSA-9612973 Autophagy 1
Partners
CISD2FEM1BGK2GYKL1MFN2MOV10L1NME3TOM20
Complex memberships
Papi complexZUC-processor complexnuage

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Drosophila Zucchini (Zuc/PLD6) is an endoribonuclease that cleaves single-stranded RNA (but not double-stranded RNA) to generate 5'-monophosphorylated products, a hallmark of mature piRNAs. Crystal structure of DmZuc at 1.75 Å reveals a positively charged, narrow catalytic groove at the dimer interface accommodating single-stranded RNA. Conserved active-site residues are essential for ribonuclease activity in vitro and for piRNA maturation and transposon silencing in vivo. Crystal structure determination (1.75 Å), in vitro endoribonuclease assay, active-site mutagenesis, in vivo piRNA and transposon analysis Nature High 23064230
2012 Mouse Zucchini homologue (mZuc/PLD6) forms a dimer in solution and possesses single-strand-specific nuclease activity. Crystal structure at 1.75 Å shows greater architectural similarity to PLD-family nucleases than to phospholipases, supporting a nuclease (rather than phospholipase) function in primary piRNA biogenesis. Crystal structure determination (1.75 Å), in vitro single-strand nuclease assay on soluble dimeric fragment Nature High 23064227
2007 Drosophila Zucchini (Zuc) localizes to the perinuclear nuage and interacts physically with the PIWI-class protein Aubergine. Loss of Zuc prevents rasiRNA (piRNA precursor) production, causing upregulation of transposable elements and failure of germline RNAi, establishing Zuc as a nuclease-domain protein required for the piRNA pathway. Co-immunoprecipitation (Zuc–Aubergine interaction), immunofluorescence localization to nuage, genetic loss-of-function with small RNA and transposon phenotype readout Developmental cell High 17543859
2011 MitoPLD (mouse PLD6) localizes to mitochondria and its knockout causes meiotic arrest, DNA damage, de-repression of retrotransposons, male sterility, and defective primary piRNA biogenesis, phenocopying piRNA pathway mutants. In mutant germ cells, mitochondria and nuage components are mislocalized around the centrosome, suggesting MITOPLD involvement in microtubule-dependent mitochondrial positioning. Knockout mouse generation, immunofluorescence/subcellular localization, small RNA sequencing, transposon expression analysis Developmental cell High 21397847
2011 MitoPLD (PLD6) at the mitochondrial surface generates the signaling lipid phosphatidic acid (PA), which recruits the phosphatase Lipin 1 to convert PA to diacylglycerol, promoting mitochondrial fission and regulating intermitochondrial cement (nuage) structure. MitoPLD and Lipin 1 have opposing effects on mitochondrial length and nuage, linking mitochondrial PA signaling to piRNA biogenesis. Knockout mouse, biochemical lipid analysis (PA generation), co-localization/fractionation, overexpression/knockdown of MitoPLD and Lipin 1 with mitochondrial morphology readout Developmental cell High 21397848
2017 In mouse growing oocytes, PLD6 depletion reduces piRNA levels by only ~50% (versus near-complete loss in males), indicating that PLD6-dependent 5'-end generation of primary piRNAs is partially compensated by other enzymes in female germ cells. MILI (PIWIL2) depletion eliminates almost all oocyte piRNAs, establishing MILI as the dominant piRNA biogenesis factor in oocytes. Knockout mice (Pld6, Mili, Miwi), small RNA sequencing and quantification in oocytes Nucleic acids research Medium 28115634
2017 Zucchini-dependent piRNA processing in Drosophila requires the helicase Armitage (Armi) and correlates with localization of piRNA precursor transcripts to nuage; recruitment of piRNA pathway factors (but not Aub, Ago3, or the nuclear RDC complex) to a heterologous RNA is sufficient to route it into the Zuc-dependent processing pathway, indicating that nuage sequestration selects piRNA biogenesis substrates. Heterologous RNA recruitment assay, genetic epistasis (zuc, armi, aub, ago3, RDC mutants), RNA localization imaging in Drosophila germ cells Genes & development Medium 29021243
2018 In Bombyx mori, loss of Zuc causes aberrant accumulation of piRNA intermediates within the mitochondrial Papi complex; recombinant Zuc processes these intermediates into mature piRNAs in vitro. Zuc acts specifically on the 3' end of piRNA intermediates (not the 5' end, which is formed by PIWI slicer activity), establishing a hierarchical biogenesis model distinct from Drosophila. Bombyx Zuc knockout, in vitro processing assay with recombinant Zuc, small RNA sequencing with 5'/3'-end analysis, Papi complex characterization Nature High 29489748
2017 Glycerol kinase-like proteins GYKL1 and GK2 interact physically with PLD6 (MitoPLD) at the mitochondrial outer membrane and, in cooperation with PLD6, induce phosphatidic acid (PA)-dependent mitochondrial clustering. Loss of either Gykl1 or Gk2 in mice causes infertility with disordered mitochondrial sheath formation in spermatids, linking the PLD6-PA axis to spermiogenesis. Co-immunoprecipitation (Gykl1/Gk2 with Pld6), mitochondrial fractionation/localization, knockout mice, phosphatidic acid measurement, mitochondrial morphology analysis Cell discovery Medium 28852571
2023 NME3, an outer mitochondrial membrane protein, is required for PLD6-induced mitochondrial tethering and clustering. NME3 binds directly to PA-exposed lipid packing defects via its N-terminal amphipathic helix; PA binding and hexamerization confer NME3 tethering activity. Nutrient starvation enhances NME3 enrichment at mitochondrial contact interfaces in a PLD6-dependent manner, promoting selective mitochondrial fusion for quality control. Co-IP/pulldown (NME3–PA interaction), lipid-binding assay, NME3 amphipathic helix mutagenesis, live-cell imaging, FRAP, NME3 KO cells The Journal of cell biology High 37584589
2025 The CRL2-FEM1B E3 ligase complex physically interacts with PLD6 through the substrate receptor FEM1B, which is itself recruited to PLD6 via direct association with the mitochondrial import receptor TOM20. FEM1B controls proteasomal turnover of PLD6; ablation of FEM1B impairs PLD6 degradation, causes mitochondrial elongation/clustering defects that phenocopy PLD6 overexpression. Proteomic analysis, Co-IP (FEM1B–PLD6, FEM1B–TOM20), structural analysis, FEM1B KO with mitochondrial morphology readout Nature chemical biology High 40263465
2023 PLD6 hydrolyzes cardiolipin to generate phosphatidic acid (PA) on the mitochondrial outer membrane, and this PA facilitates membrane fusion of LDLR+ endocytic vesicles with mitochondria. CISD2 on the outer mitochondrial membrane binds the cytosolic tail of LDLR, tethering LDLR+ vesicles to mitochondria, while PLD6-derived PA drives the actual membrane fusion event, delivering LDL-cholesterol to mitochondria for steroidogenesis bypassing lysosomes. Genome-wide shRNA screen, Co-IP (CISD2–LDLR), lipid biochemistry (PA measurement), live-cell imaging, PLD6 KO/knockdown with vesicle fusion and cholesterol trafficking readout Nature cell biology High 37277481
2021 PLD6 loss-of-function in mice primarily silences retrotransposons at the posttranscriptional level (RNA degradation) rather than through DNA methylation. In Pld6 mutant prospermatogonia, most retrotransposons show increased RNA without major DNA methylation loss, whereas DNA methylation deficiency (Dnmt3l KO) has limited immediate transcriptional impact; long-term DNA hypomethylation caused by Pld6 mutation leads to increased retrotransposon expression in later meiotic stages. Pld6 KO and Dnmt3l KO mice, DNA methylation profiling, RNA-seq, nascent RNA quantification, cleaved RNA-end profiling, double KO epistasis PLoS genetics High 28749988
2021 MOV10L1 interacts physically with PLD6; a single amino acid substitution V229E in the MOV10L1 N-terminal region (yama mutation) reduces this interaction, causing defects in pre-pachytene piRNA biogenesis and meiotic arrest, establishing the MOV10L1–PLD6 interaction as functionally required for piRNA 5'-end generation. Mov10l1 point-mutant mouse (V229E), Co-IP (MOV10L1–PLD6), small RNA sequencing, conditional KO epistasis PLoS genetics Medium 33635934
2022 Zebrafish pld6 is a germline-specific regulator of mitochondrial fusion; pld6 knockout mutants exhibit impaired mitochondrial fusion in germline stem and progenitor cells, failure of GSPC differentiation, apoptosis of GSPCs, masculinization, and infertility, accompanied by defects in piRNA biogenesis and transposon de-repression. CRISPR/Cas9 pld6 knockout zebrafish, mitochondrial morphology imaging, small RNA sequencing, transposon expression analysis Advanced science Medium 36257818
2022 Within the piRNA 3'-end formation pathway, the ZUC-processor complex defines a 'Goldilocks zone' interval on pre-piRNA intermediates where cleavage preferentially occurs in front of Uridine; this sequence preference, combined with PIWI-protein length preferences, ensures a single dominant piRNA 3'-end in both flies and mice. Deep sequencing of piRNA intermediates in Drosophila and mouse, biochemical analysis of cleavage site preferences iScience Medium 35669519
2017 In Bombyx mori BmN4 cells, silkworm Zuc (BmZuc) localizes to mitochondria; molecular dissection shows the conserved mitochondrial localization sequence, RGV motif, PLDc2 domain, and HKD motif are each required for mitochondrial targeting. Knockdown of BmZuc does not affect nuage localization of other piRNA pathway components, but BmZuc itself depends on piRNA pathway components for proper localization. Subcellular fractionation, immunofluorescence, domain-deletion constructs, RNAi knockdown in BmN4 cells Biochemical and biophysical research communications Medium 28942151
2021 Endogenous PLD6 in mouse testes localizes to the Golgi apparatus (partially overlapping with the cis-Golgi marker GM130) of pachytene spermatocytes and developing spermatids, specifically in flattened medial-Golgi cisternae, rather than to mitochondria as observed for ectopically overexpressed PLD6. PLD6 also interacts physically with tesmin, a testis-specific protein required for spermatogenesis. Validated anti-PLD6 antibodies, immunofluorescence, correlative light and electron microscopy, Co-immunoprecipitation (PLD6–tesmin), GM130 co-staining Cell and tissue research Medium 33783608
2016 PLD6 mediates MYC-driven inhibition of YAP/TAZ in mammary epithelial cells by altering mitochondrial fusion/fission dynamics downstream of MYC, which strains cellular energy and activates AMPK; AMPK in turn inhibits YAP/TAZ co-activators. PLD6 is identified as the effector linking MYC-induced energy stress to mitochondrial dynamics and YAP/TAZ suppression. Genetic epistasis (PLD6 KD/OE), AMPK activity assay, YAP/TAZ reporter, mitochondrial morphology analysis, mouse mammary tumor models Cancer cell Medium 26678338
2023 TurboID proximity labeling of Zuc (PLD6) in the Drosophila ovary defines the Zuc-proximal proteome, confirming enrichment at the outer mitochondrial membrane and identifying novel candidate interactors including chaperone-function proteins and endomembrane/vesicle transport proteins. Knockdown of several proximal candidates causes transposable element de-repression, validating their functional relevance to piRNA biogenesis. TurboID proximity labeling, quantitative mass spectrometry, RNAi knockdown with transposon de-repression readout Development (Cambridge, England) Medium 36762624
2026 NME3 interacts with PLD6/MitoPLD to generate phosphatidic acid (PA) from cardiolipin on the outer mitochondrial membrane of damaged/depolarized mitochondria. This NME3-PLD6-derived PA is required to position MFN2 in proximity to PINK1 for ubiquitin phosphorylation on MFN2, enabling feedforward PRKN/parkin recruitment and mitophagy. Loss of NME3 impairs this PA signal, causing aberrant mitochondria-ER tethering that blocks MFN2 access to PINK1. Co-IP (NME3–PLD6), FRET/proximity ligation assay, PA generation assay, NME3 KO and KD with p-S65-ubiquitin and PRKN-binding readout, transmission electron microscopy Autophagy Medium 41640016
2025 PLD6 depletion in colorectal cancer cells suppresses mitochondrial respiration (reduces mitochondrial length, membrane potential, calcium, and ROS), inhibits the TCA cycle and oxidative phosphorylation, lowers intracellular citrate and acetyl-CoA levels, and thereby reduces β-catenin acetylation by CBP/P300, destabilizing β-catenin and suppressing Wnt/β-catenin signaling. PLD6 thus acts as an oncogenic switch linking mitochondrial metabolism to Wnt pathway activation via acetyl-CoA. PLD6 KD/KO in CRC cells, mitochondrial respiration assays, metabolomics (TCA intermediates, acetyl-CoA), β-catenin acetylation assay, Co-IP, subcutaneous and orthotopic tumor models Experimental & molecular medicine Medium 40259095
2024 TRABD forms complexes with MFN2, MIGA2, and PLD6 at the mitochondrial outer membrane to facilitate mitochondrial fusion; PLD6 is thus a component of a multi-protein fusion complex. Co-immunoprecipitation (TRABD with MFN2, MIGA2, PLD6), overexpression/loss-of-function with mitochondrial morphology readout Cell reports Low 38843396
2017 PLD6 surface expression marks undifferentiated spermatogonia (SSCs) in mouse testes; PLD6 is primarily localized to the spermatogonial membrane, providing a cell-surface marker for SSC enrichment. Immunofluorescence, subcellular fractionation, magnetic-activated cell sorting, proteomics of SSCs Journal of cellular and molecular medicine Low 25352495
2016 Human PLD6 (MitoPLD) can be produced and purified as a recombinant protein retaining in vitro endonuclease activity against RNA transcripts, confirming the nuclease function of the human orthologue. Recombinant protein production, purification, in vitro endonuclease activity assay Methods in enzymology Medium 28063496

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature 278 23064230
2011 piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling. Developmental cell 269 21397848
2012 The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature 265 23064227
2011 MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline. Developmental cell 251 21397847
2007 zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Developmental cell 250 17543859
2015 A MYC-Driven Change in Mitochondrial Dynamics Limits YAP/TAZ Function in Mammary Epithelial Cells and Breast Cancer. Cancer cell 122 26678338
2020 BNIP3L/Nix-induced mitochondrial fission, mitophagy, and impaired myocyte glucose uptake are abrogated by PRKA/PKA phosphorylation. Autophagy 86 33044904
2010 Altered DNA methylation in leukocytes with trisomy 21. PLoS genetics 85 21124956
1971 The molecular defect in a protein (CRA) found in gamma-1 heavy chain disease, and its genetic implications. Proceedings of the National Academy of Sciences of the United States of America 78 4100047
2018 Comparative whole genome DNA methylation profiling of cattle sperm and somatic tissues reveals striking hypomethylated patterns in sperm. GigaScience 55 29635292
2016 Biogenesis of diverse plant phasiRNAs involves an miRNA-trigger and Dicer-processing. Journal of plant research 52 27900550
2017 Roles of MIWI, MILI and PLD6 in small RNA regulation in mouse growing oocytes. Nucleic acids research 48 28115634
2023 Delivery of low-density lipoprotein from endocytic carriers to mitochondria supports steroidogenesis. Nature cell biology 47 37277481
2017 Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility. Cell discovery 41 28852571
2018 Hierarchical roles of mitochondrial Papi and Zucchini in Bombyx germline piRNA biogenesis. Nature 40 29489748
2017 Low-intensity extracorporeal shock wave therapy promotes myogenesis through PERK/ATF4 pathway. Neurourology and urodynamics 37 28763567
2017 Zucchini-dependent piRNA processing is triggered by recruitment to the cytoplasmic processing machinery. Genes & development 36 29021243
2017 Switching of dominant retrotransposon silencing strategies from posttranscriptional to transcriptional mechanisms during male germ-cell development in mice. PLoS genetics 34 28749988
2014 Establishment of a proteome profile and identification of molecular markers for mouse spermatogonial stem cells. Journal of cellular and molecular medicine 32 25352495
2019 Genome-wide DNA methylation analysis in ankylosing spondylitis identifies HLA-B*27 dependent and independent DNA methylation changes in whole blood. Journal of autoimmunity 30 31128893
1998 Differential responses of estrogen target tissues in rats including bone to clomiphene, enclomiphene, and zuclomiphene. Endocrinology 26 9724022
2011 piRNAs meet mitochondria. Developmental cell 24 21397839
1995 Codominant effects of the fatty (fa) gene during early development of obesity. The American journal of physiology 24 7840172
2018 Transcriptional regulation of P63 on the apoptosis of male germ cells and three stages of spermatogenesis in mice. Cell death & disease 23 29362488
2018 Large plasmidome of dairy Lactococcus lactis subsp. lactis biovar diacetylactis FM03P encodes technological functions and appears highly unstable. BMC genomics 22 30119641
2020 Promoter hypermethylation of PIWI/piRNA pathway genes associated with diminished pachytene piRNA production in bovine hybrid male sterility. Epigenetics 21 32141383
2023 NME3 binds to phosphatidic acid and mediates PLD6-induced mitochondrial tethering. The Journal of cell biology 19 37584589
2022 A Germline-Specific Regulator of Mitochondrial Fusion is Required for Maintenance and Differentiation of Germline Stem and Progenitor Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 36257818
1987 Gap junction modulation in rat uterus. III. Structure-activity relationships of estrogen receptor-binding ligands on myometrial and serosal cells. Biology of reproduction 15 3593845
2021 yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis. PLoS genetics 14 33635934
2020 Regenerating Urethral Striated Muscle by CRISPRi/dCas9-KRAB-Mediated Myostatin Silencing for Obesity-Associated Stress Urinary Incontinence. The CRISPR journal 14 33346712
2018 The effect of low-intensity extracorporeal shockwave therapy in an obesity-associated erectile dysfunction rat model. BJU international 14 29573106
2016 Kc167, a widely used Drosophila cell line, contains an active primary piRNA pathway. RNA (New York, N.Y.) 14 27789612
2019 Microenergy acoustic pulses induced myogenesis of urethral striated muscle stem/progenitor cells. Translational andrology and urology 13 32133280
1983 The estrogenic effects of clomiphene during the neonatal period in the rat. Journal of steroid biochemistry 13 6406767
2017 Phospholipase D Family Member 6 Is a Surface Marker for Enrichment of Undifferentiated Spermatogonia in Prepubertal Boars. Stem cells and development 12 29113556
2016 Measuring Phospholipase D Enzymatic Activity Through Biochemical and Imaging Methods. Methods in enzymology 12 28063496
2021 Crystal Structure of a Phospholipase D from the Plant-Associated Bacteria Serratia plymuthica Strain AS9 Reveals a Unique Arrangement of Catalytic Pocket. International journal of molecular sciences 11 33809980
2018 Genome-wide association for testis weight in the diversity outbred mouse population. Mammalian genome : official journal of the International Mammalian Genome Society 11 29691636
2025 TOM20-driven E3 ligase recruitment regulates mitochondrial dynamics through PLD6. Nature chemical biology 10 40263465
2022 Hierarchical length and sequence preferences establish a single major piRNA 3'-end. iScience 10 35669519
2016 Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment. BJU international 9 27511863
2023 Expression of Phospholipase D Family Member 6 in Bovine Testes and Its Molecular Characteristics. International journal of molecular sciences 8 37569546
2020 A Comprehensive Molecular and Clinical Analysis of the piRNA Pathway Genes in Ovarian Cancer. Cancers 8 33374923
2017 Molecular characterization of mitochondrial Zucchini and its relation to nuage-piRNA pathway components in Bombyx mori ovary-derived BmN4 cells. Biochemical and biophysical research communications 7 28942151
2024 TRABD modulates mitochondrial homeostasis and tissue integrity. Cell reports 6 38843396
2021 Cellular and subcellular localization of endogenous phospholipase D6 in seminiferous tubules of mouse testes. Cell and tissue research 6 33783608
2018 In Situ Activation and Preservation of Penile Progenitor Cells Using Icariside II in an Obesity-Associated Erectile Dysfunction Rat Model. Stem cells and development 6 29179669
2024 Phospholipase D, a Novel Therapeutic Target Contributes to the Pathogenesis of Neurodegenerative and Neuroimmune Diseases. Analytical cellular pathology (Amsterdam) 5 38487684
2021 Genes underlying the evolution of tetrapod testes size. BMC biology 5 34407824
2025 Phospholipase D6 activates Wnt/β-catenin signaling through mitochondrial metabolic reprogramming to promote tumorigenesis in colorectal cancer. Experimental & molecular medicine 4 40259095
2025 Sirt6 deficiency exacerbates angiotensin II-induced lipid nephrotoxicity by affecting PLD6-derived cardiolipin metabolism in podocytes. Cellular signalling 4 40355014
2023 In vivo profiling of the Zucchini proximal proteome in the Drosophila ovary. Development (Cambridge, England) 4 36762624
2019 Change in the Binding of [11C]BU99008 to Imidazoline I2 Receptor Using Brain PET in Zucker Rats. Molecular imaging and biology 4 29736564
2014 Is zucchini a phosphodiesterase or a ribonuclease? Biomedical journal 4 25179713
1996 A rat homolog of the mouse deafness mutant jerker (je). Mammalian genome : official journal of the International Mammalian Genome Society 4 8661723
2025 DNA methylation dictates histone modifications in developing male germ cells in the mouse. Nucleic acids research 3 41273173
2024 Lycopene and Garcinia cambogia Induce White-to-Brown Adipose Differentiation: An Innovative Strategy to Curb Obesity. Pharmaceuticals (Basel, Switzerland) 3 39204091
2022 PIWI-Interacting RNA Pathway Genes: Potential Biomarkers for Clear Cell Renal Cell Carcinoma. Disease markers 3 35273654
2022 First characterization of PIWI-interacting RNA clusters in a cichlid fish with a B chromosome. BMC biology 3 36127679
2012 Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits. Physiological genomics 3 22968639
2012 Fucosyl neoglycoprotein binds to mouse epididymal spermatozoa and inhibits sperm binding to the egg zona pellucida. Andrologia 3 22998388
2022 Beneficial effects of a prescription home-prepared diet and of zucchini on urine calcium oxalate supersaturation and urinary parameters in adult cats. Journal of feline medicine and surgery 2 35142590
2021 Ileal transposition helps to regulate plasma hepatokine levels in obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. Scientific reports 2 33833309
2012 Expression, purification, crystallization and preliminary X-ray crystallographic analysis of Zucchini from Drosophila melanogaster. Acta crystallographica. Section F, Structural biology and crystallization communications 2 23143246
2025 In Vivo Application of TurboID-based Proximity Labeling in Drosophila melanogaster. Journal of visualized experiments : JoVE 1 40587414
2014 Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats. PloS one 1 24498189
2014 Expression of hp1 family genes and their plausible role in formation of flamenco phenotype in D. melanogaster. Biochemistry. Biokhimiia 1 25540013
2026 A novel 2D and 3D model for primary adrenocortical carcinoma of advanced and metastasized stage co-secreting cortisol, aldosterone, testosterone, 18-oxocortisol and 18-hydroxycortisol. Endocrine-related cancer 0 41528016
2026 PRKN activation for mitophagy requires an NME3-regulated phosphatidic acid signal that separates mitochondria from endoplasmic reticulum tethering. Autophagy 0 41640016
2025 Morphological and immunological approach for studying the distribution pattern of mitochondria and germ granules during oogenesis of the guppy (Poecilia reticulata). Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 0 40684887
2024 Association of overexpression of PLD6, CHRAC1 and PDCD5 with type 2 diabetes mellitus. Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina 0 39526719
2017 Chow fed UC Davis strain female Lepr fatty Zucker rats exhibit mild glucose intolerance, hypertriglyceridemia, and increased urine volume, all reduced by a Brown Norway strain chromosome 1 congenic donor region. PloS one 0 29211750

Missed literature

Know a paper Affinage missed for PLD6? Flag it for the maintainers and the community.

No submissions yet.