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- W4387297101 abstract "Sphingomyelin plays a key role in cellular cholesterol homeostasis by binding to and sequestering cholesterol in the plasma membrane. We discovered that synthesis of very long chain (VLC) sphingomyelins is inversely regulated by cellular cholesterol levels; acute cholesterol depletion elicited a rapid induction of VLC-sphingolipid synthesis, increased trafficking to the Golgi apparatus and plasma membrane, while cholesterol loading reduced VLC-sphingolipid synthesis. This sphingolipid-cholesterol metabolic axis is distinct from the sterol responsive element binding protein pathway as it requires ceramide synthase 2 (CerS2) activity, epidermal growth factor receptor signaling, and was unaffected by inhibition of protein translation. Depletion of VLC-ceramides reduced plasma membrane cholesterol content, reduced plasma membrane lipid packing, and unexpectedly resulted in the accumulation of cholesterol in the cytoplasmic leaflet of the lysosome membrane. This study establishes the existence of a cholesterol-sphingolipid regulatory axis that maintains plasma membrane lipid homeostasis via regulation of sphingomyelin synthesis and trafficking." @default.
- W4387297101 created "2023-10-04" @default.
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- W4387297101 date "2023-10-03" @default.
- W4387297101 modified "2023-10-16" @default.
- W4387297101 title "Cholesterol-dependent homeostatic regulation of very long chain sphingolipid synthesis" @default.
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- W4387297101 doi "https://doi.org/10.1083/jcb.202308055" @default.
- W4387297101 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37787764" @default.
- W4387297101 hasPublicationYear "2023" @default.
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