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Lecture "From fat to signals of life & death: lipid droplets as managers of inflammation and ferroptosis"

Prof. Toni Petan, Jožef Stefan Institute, Ljubljana, Slovenia

Lipid droplets (LDs) are cytosolic fat storage organelles present in all eukaryotic cells. They have a unique structure among organelles consisting of a dense hydrophobic core of neutral lipids, mostly triglycerides and cholesteryl esters, surrounded by a single layer of phospholipids decorated with various proteins. Often labeled merely as passive fat storage repositories, they in fact have a remarkably dynamic life cycle. Being formed within the endoplasmic reticulum membrane as vessels for neutral lipids they emerge into the cytosol where they grow, fuse, shrink and engage in contacts with organelles to exchange proteins and lipids. LD breakdown is mediated by elaborate enzymatic mechanisms and several forms of autophagy to fine-tune the distribution of lipids to various destinations in the cell. Remarkably, emerging studies suggest that LDs are involved in cellular responses to various energy and redox imbalances, including those induced by nutrient and oxygen deprivation, or elevated nutrient availability and oxidative stress. Our recent work in cancer cell demonstrates that LDs also manage the trafficking of polyunsaturated fatty acids (PUFAs) during stress. On the one hand, we find that the incorporation of PUFAs into triglycerides stored within LDs and their release via adipose triglyceride lipase (ATGL) are required for the conversion of PUFAs into inflammatory lipid mediators, including the pro-tumourigenic eicosanoids. On the other hand, when cellular redox defenses are compromised, LDs become major determinants of life and death, acting as antioxidant organelles that manage the storage and release of oxidation-prone PUFAs to prevent membrane lipid peroxidation and ferroptotic cell death. Thus, LDs act as major cellular hubs that control lipid oxygenation pathways responsible for both inflammatory signaling and ferroptosis in cancer and beyond.

Toni Petan received his PhD in Biochemistry and Molecular Biology from the University of Ljubljana, Slovenia, working on protein engineering and membrane enzymology. Following his postdoc studies in cancer cell biology at Harvard Medical School, USA, he returned to Slovenia and formed a research group at Jožef Stefan Institute in Ljubljana, blending his love for lipids, membranes and cancer cell biology and metabolism. His current research is focused on a fascinating, long-neglected fat storage organelle, the lipid droplet, and its roles in cellular stress responses. His group at Jožef Stefan Institute is working on deciphering fundamental questions regarding the function of lipid droplets in fatty acid metabolism and inflammatory signalling, their capacity to regulate membrane lipid peroxidation and ferroptotic cell death, and their interplay with autophagic responses to nutrient stress.

IPHYS contact person: Ondřej Kuda,