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Talk by Birol Cabukusta

Title: "Lipid exchanges between organelles at membrane contact sites"
Occasion: SFB Seminar
Host: Joost Holthuis
Start: 20.04.2023 - 16:15
Location: CellNanOs 38/201

About the speaker: Birol Cabukusta conducts research in the Medical Center at the University of Leiden, Netherlands.

Abstract of the talk: Heterogeneous distribution of proteins and lipids into various membrane-bound organelles is fundamental to eukaryotic life. The uneven distribution of lipids among organelles is achieved mainly by a group of lipid transfer proteins (LTPs) that are specialized in non-vesicular trafficking of lipids between organelles. Despite achieving a great understanding of these proteins in the last years, our knowledge of LTPs is still limited. To better understand this group of proteins, we created a gene knockout library targeting human LTPs based on the CRISPR/Cas9 technology. Lipidomics analysis of the LTP knockout library revealed many known and unknown proteins as regulators of cellular lipid levels. Among these, we found ORP9 and ORP11 knockout cells with lowered sphingomyelin levels. We demonstrate that ORP9 and ORP11 -two proteins with no known function in sphingolipid metabolism- dimerize with each other to localize at ER-trans Golgi membrane contact sites to exchange phosphatidylserine (PS) and phosphatidylinositol-4-phosphate (PI(4)P) between the two organelles. Using click chemistry tools and organelle isolation techniques, we further show that PS/PI(4)P exchange by ORP9-ORP11 is critical for sphingomyelin synthesis in the Golgi apparatus. Our work describes one of the few instances where coupling of mammalian phospholipid and sphingolipid metabolisms takes place at membrane contact sites.