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Propose that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD.
MitoPLD performs a critical function in a pathway that creates a specialized form of RNAi required by developing spermatocytes to suppress transposon mobilization during meiosis.
Data suggest that mitochondrial-surface phosphatidic acid generated by MitoPLD/Zuc recruits or activates nuage components critical for piRNA production.
PLD6, aka (show NEUROG1 Proteins) MitoPLD, encodes an N-terminal mitochondrial localization sequence, localizes to the outer mitochondrial surface, generates phosphatidic acid, a signaling lipid, and triggers trans-mitochondrial association; involved in mitochondrial fusion.
MIWI (show PIWIL1 Proteins) (or PIWIL1 (show PIWIL1 Proteins)) depletion had a smaller effect. In oocytes lacking PLD6 (or ZUCCHINI or MITOPLD), a mitochondrial nuclease (show DCLRE1C Proteins)/phospholipase involved in piRNA biogenesis in male germ cells, the piRNA level was decreased to 50% compared to wild-type.
Drp1 (show CRMP1 Proteins) binds a mitochondrial enzyme that produces phosphatidic acid, MitoPLD, and regulates mitochondrial division.
The Dnmt3l (show TRDMT1 Proteins) mutation greatly reduced DNA methylation (show HELLS Proteins) levels at most retrotransposons, but its impact on their RNA abundance was limited in prospermatogonia. In Pld6 mutant germ cells, although only a few retrotransposons exhibited reduced DNA methylation (show HELLS Proteins), many showed increased expression at the RNA level.
crystal structure of mZuc at 1.75 A resolution indicates greater architectural similarity to phospholipase-D family nucleases than to phospholipases; data suggest that the Zucchini proteins act in primary piRNA biogenesis as nucleases, perhaps generating the 5' ends of primary piRNAs.
Results indicate a conserved role for MITOPLD/Zuc in the piRNA pathway and link mitochondrial membrane metabolism/signaling to small RNA biogenesis.
Cardiolipin hydrolase present at the mitochondrial outer membrane required both for mitochondrial fusion and piRNA metabolic process. Acts by catalyzing the hydrolysis of cardiolipin (diphosphatidylglycerol) to form phosphatidate (phosphatidic acid or PA) at the mitochondrial outer membrane surface, promoting mitochondrial fusion. The production of phosphatidate also regulates the piRNA metabolic process by promoting recruitment and/or activation of components of the meiotic nuage, also named P granule, a critical step for primary biogenesis of piRNAs. Required during spermatogenesis to repress transposable elements and prevent their mobilization via its role in the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons (By similarity).
, choline phosphatase 6
, mitochondrial cardiolipin hydrolase
, mitochondrial phospholipase
, phosphatidylcholine-hydrolyzing phospholipase D6
, phospholipase D6
, protein zucchini homolog
, novel Phospholipase D Active site motif-containing protein
, Probable phospholipase D family member FLJ33580 homolog
, probable phospholipase D family member FLJ33580 homolog