ArticleCell2024
PLD3 and PLD4 synthesize S,S-BMP, a key phospholipid enabling lipid degradation in lysosomes.
Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed.
- Pathogenic variants of the mitochondrial copper chaperones SCO1 and SCO2 reshape their respective interactomes and disrupt cellular phospholipid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Batten disease protein CLN8 enables a non-canonical phospholipid synthesis pathway.Nature cell biology · 2026Article
- CLN8 recycles glycerol backbones for BMP.Nature cell biology · 2026Article
- The Batten disease protein CLN8 is a stereospecific acyltransferase in bis(monoacylglycero)phosphate biosynthesis.Nature cell biology · 2026Article
- Lysosomal Dysfunction Is Associated With Intervertebral Disc Degeneration: Multiomics and Machine Learning Identify Molecular Subtypes and Hub Genes.The journal of gene medicine · 2026Article
- sPLAScience advances · 2026Article
- Shared lipidome and proteome signatures of frontotemporal lobar degeneration and Alzheimer's disease.Research square · 2026Article
- Restoration of impaired lysosomal function mitigates drusen-like deposit formation and cell death in Malattia Leventinese.JCI insight · 2026Article
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.Cell reports · 2026Article
- Astrocytic ACSBG1 depletion improves lipid-cytokine signaling and attenuates α-Synuclein pathology in a Parkinson's disease mouse model.bioRxiv : the preprint server for biology · 2026Article
- PLD3-mediated Mitophagy Attenuates Neuronal Ferroptosis and Promotes Functional Recovery after Spinal Cord Injury.Molecular neurobiology · 2026Article
- Lysosomes contribute to the synthesis of tricarboxylic acid-related metabolites in the hippocampus.Life metabolism · 2026Article
- Lipofuscin accumulation in aging and CLN1 is associated with deficient de-S-acylation, lyso-mitochondrial dysfunction, and lipid dyshomeostasis.Acta neuropathologica · 2026Article
- Targeting the PGRN-BMP Lysosomal Axis With NPs@PGRN Reverses Immunometabolic Dysfunction in Chronic Septic Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploring the PLD1-tau interaction in Frontotemporal Dementia.bioRxiv : the preprint server for biology · 2026Article
- Deficient de-S-acylation in aging and CLN1 contributes to lyso-mitochondrial dysfunction, lipid dyshomeostasis, and resultant lipofuscin biogenesis.Research square · 2026Article
- Unveiling Lipid Dysregulation: Lipidomics of Mouse Brain and Isolated Myelin in Niemann-Pick Disease Type C1.bioRxiv : the preprint server for biology · 2026Article
- Microbial tryptophan metabolism activates host lysosomal activity to facilitate lipid breakdown.PLoS biology · 2026Article
- The Phospholipid Bis(monoacylglycero)Phosphate Confers Antitumour Immunogenicity to Exosomes Secreted by Dendrogenin A, Which Activates Its Biosynthesis in Tumour Cells.Journal of extracellular vesicles · 2026Article
- Spatially resolved transcriptome-metabolome integration reveals region-specific glial lipid dysregulation associated with Alzheimer's pathology.bioRxiv : the preprint server for biology · 2026Article
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Abstract
Bis(monoacylglycero)phosphate (BMP) is an abundant lysosomal phospholipid required for degradation of lipids, particularly gangliosides. Alterations in BMP levels are associated with neurodegenerative diseases. Unlike typical glycerophospholipids, lysosomal BMP has two chiral glycerol carbons in the S (rather than the R) stereo-conformation, protecting it from lysosomal degradation. How this unusual and yet crucial S,S-stereochemistry is achieved is unknown. Here, we report that phospholipases D3 and D4 (PLD3 and PLD4) synthesize lysosomal S,S-BMP, with either enzyme catalyzing the critical glycerol stereo-inversion reaction in vitro. Deletion of PLD3 or PLD4 markedly reduced BMP levels in cells or in murine tissues where either enzyme is highly expressed (brain for PLD3; spleen for PLD4), leading to gangliosidosis and lysosomal abnormalities. PLD3 mutants associated with neurodegenerative diseases, including risk of Alzheimer's disease, diminished PLD3 catalytic activity. We conclude that PLD3/4 enzymes synthesize lysosomal S,S-BMP, a crucial lipid for maintaining brain health.
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