On Monday morning, October 9, Harmeet Malhi, MD, of the Mayo Clinic, described her group’s work that has identified a novel pathway for the formation of lipotoxic extracellular vesicles (EVs). She noted that while lipotoxic hepatocyte-derived EVs are key mediators of cell-to-cell communication in nonalcoholic steatohepatitis, the cellular machinery for the biogenesis of lipotoxic EVs has remained undefined. Recently, her group has demonstrated that palmitate (PA)-induced EVs are enriched in C16:0 ceramide, are consistent with exosomes formed within the multivesicular body (MVB), and their release depends on the synthesis of ceramide at the endoplasmic reticulum (ER). She noted that STARD11, a ceramide transport protein, mediates the trafficking of newly formed ceramide from the ER to the Golgi, but that its role in the transport of newly formed ceramide from the ER to the MVB is unknown. The aim of the work reported here was to test the hypothesis that the ceramide transport protein, STARD11, is necessary for the transport of ceramide from the ER to the MVB, thus mediating the biogenesis of lipotoxic EVs. The results suggest that STARDT11 mediates the biogenesis of PA-induced ceramide-enriched EVs due to the transport of newly synthesized ceramide from the ER to the MVB. The group has identified a novel pathway for the formation of lipotoxic EVs, and future work will focus on the functional consequences of this pathway. The American Society for Exosomes and Microvesicles (ASEMV) 2017 Annual Meeting was held October 8-12 at the Asilomar Conference Grounds in Pacific Grove, California.
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