Role of Very Long-Chain Fatty Acyl-Ceramides in Endocytic Uptake

VLC fatty acyl-ceramides (VLCA-Cers) are specifically required for constriction of endocytic invaginations at ER sterol exit sites (ERSES), with Cer synthase directly interacting with endocytic machinery.

• Why it matters: Endocytic budding depends on local sterol supply and actin-driven membrane remodeling, but how ceramide lipids are locally produced and delivered at ER-endocytic contact sites remained unclear.
• What they did: The study identified Fat1 as a C20–C26 very long-chain fatty acid transporter and acyl-CoA synthetase, then mapped VLC-FA pathways and used molecular dynamics plus live-cell imaging with a ceramide probe.
• The result: ORPs Osh1 and Osh3 contribute to Cer export from ER-ECS, and their depletion recapitulates the endocytic defects seen when VLCFA-Cer is absent, supporting a direct role in membrane remodeling.

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