ArticleNature communications2025
Nuclear receptor signaling regulates compartmentalized phosphatidylcholine remodeling to facilitate thermosensitive lipid droplet fusion.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Structural modeling supports an interaction between thebioRxiv : the preprint server for biology · 2026Article
- Rethinking LPCAT3 roles in human disease: broadening perspectives beyond ferroptosis.Cell death & disease · 2026Review
- Metabolic hubs in reproduction: The regulatory network of lipid droplets in gamete and embryo physiology (Review).International journal of molecular medicine · 2026Review
- Integrated analysis of fecal microbiome and serum metabolome reveals the profiling of gut microbiota-related metabolites in rats and mice subjected to prolonged exposure to a high-humidity environment.Frontiers in cellular and infection microbiology · 2026Article
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5 authors.
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Abstract
Lipid droplet (LD) fusion plays a key role in cellular fat storage. How the phospholipid monolayer membrane of LD functions in fusion, however, is poorly understood. In Caenorhabditis elegans, loss of cytochrome P450 protein CYP-37A1 causes de-repression of nuclear receptor DAF-12, promoting thermosensitive LD fusion. Here, we report that in cyp-37A1 mutants, DAF-12 up-regulates the transcription and LD localization of seven fatty acid desaturases (FAT-1 to FAT-7) and a lysophosphatidylcholine acyltransferase 3 (LPCAT3) homolog MBOA-6. LD-targeting of these enzymes increases phosphatidylcholine (PC) containing ω-3 C20 polyunsaturated fatty acids, which are essential for thermosensitive fusion. ω-3 C20-PC increase LD membrane fluidity, as does high ambient temperature. Lowering LD membrane fluidity by a chemical membrane rigidifier attenuates thermosensitive fusion; ectopic targeting of ω3 desaturase FAT-1 or MBOA-6 to LDs increases fusion kinetics and thermosensitivity. Furthermore, human LPCAT3 localizes to LDs, positively regulates LD size in human cells and facilitates thermosensitive fusion in C. elegans. These results demonstrate that DAF-12 signaling regulates compartmentalized membrane remodeling and fluidization to facilitate conserved thermosensitive LD fusion.
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