Presents phospholipase and nuclease activities, depending on the different physiological conditions (PubMed:17028579, PubMed:24599962, 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:24599962, 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). a cardiolipin + H2O = 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) + a 1,2-diacyl-sn-glycero-3-phosphate + H(+) MYC stimulates its phospholipase activity (PubMed:26678338). MIGA1 and MIGA2 increase PLD6 self-association affinity and affects the homodimer conformation facilitating its phospholipase activity over the nuclease activity (PubMed:26711011). Single stranded DNA (ssDNA) hydrolase activity does not depend upon, but is stimulated by the presence of Ca(2+) and Mn(2+) (By similarity). Homodimer (PubMed:17028579). Interacts with MOV10L1 (By similarity). Interacts with MIGA1 and MIGA2; possibly facilitating homodimer formation (PubMed:26711011). Interacts with GK2 (PubMed:28852571). Localization in the mitochondrial outer membrane is found in different cell types where phospholipase is the predominant activity, however, in pachytene spermatocytes and spermatids of mouse testes where nuclease activity is predominant, localization is restricted to the Golgi, suggesting this enzyme is localized in different subcellular compartments depending on the role (phospholipase or nuclease) it needs to play in each cell type and developmental stage. Predominantly expressed in testis and ovary, but not limited to gonads (at protein level) (PubMed:17028579, PubMed:21397847). It is also found in brain, heart, pituitary gland, prostate, pancreas, thyroid, bone marrow, lung and muscle (PubMed:21397847). In contrast to other members of the phospholipase D family, contains only one PLD phosphodiesterase domain, suggesting that it has a single half-catalytic and requires homodimerization to form a complete active site. Belongs to the phospholipase D family. MitoPLD/Zucchini subfamily. Evidence for subcellular location in the Golgi was determined in pachytene spermatocytes and spermatids in mouse testes. They observe that the ectopically expressed PLD6 protein was localized to the mitochondria in PLD6-transfected cells. Authors claim a possible explanation for the contradictory results is that previous studies have reported the localization of exogenous PLD6, but not endogenous PLD6, in cultured cells. The reason for differences observed in subcellular localization of exogenous and endogenous PLD6 is not clear but one attributable reason may be that different types of anti-PLD6 antibodies have been used in previous studies.