Nuclear Lipid droplets are a dynamic cellular organelle

VES LOSADA, ANA

Orlando, Florida, USA

Workshop; Workshop of Biological Droplets (http://emnmeeting.org/Americas/droplets/biological-droplets/; 2017

EMN Americas Meetings (Energy Materials Nanotechnolog)

In eukaryotic cells under normal cell-physiologic conditions, hydrophobic molecules as neutral lipids (TAG: triacylglycerides, CE: cholesterol esters and C: cholesterol) are stored and organized as Lipid Droplets (LD). LD are mainly located in the cytosol (cLD), and within the nucleus we have already identified a small LD population (nLD) that corresponds to 2-10% of total cellular LD (cLD + nLD) (1,2). nLD correspond to a small hydrophobic nuclear domain, constituted by few and small LD that are randomly distributed within the nucleus. nLD would be built up around a hydrophobic core of TAG and CE enriched in oleic acid (OA) and surrounded by a monolayer of polar lipids, cholesterol and proteins. nLD could be involved in nuclear-lipid homeostasis and serve as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signaling pathways, ligands for transcription factors, and enzymes of lipid metabolism and nuclear processes. Thus, within the nucleus, the lipids would have two main locations: the nuclear envelope?composed mainly of glycerophospholipids, sphingolipids, and C?and the nLD (containing principally TAG, CE, C, and polar lipids). Both of these domains would constitute alternative lipid sources with different chemical compositions, physical properties, potential functions, and possible regulatory characteristics (1).The aim of the present work was to determine if nLD constituted a dynamic domain. Experiments were performed in a hepatic cellular model of isolated rat hepatocytes and HepG2 cells (human hepatoma cell line). OA added to rat hepatocytes or HepG2 cells in culture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PL content and in cLD and nLD numbers and sizes. LD increments were reversed on exclusion of OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thus lipid biosynthesis. Under all conditions, nLD corresponded to a small population of total cellular LD. The anabolism triggered by OA, involving morphologic and size changes within the cLD and nLD populations, was reversed by a net balance of catabolism, upon eliminating OA from the cell culture. These catabolic processes included lipolysis and the mobilization of hydrolyzed FA from the LD to cytosolic-oxidation sites. These results would imply that nLD are actively involved in nuclear processes that include lipids.In conclusion, nLD are a dynamic nuclear domain since they are modified by OA through a reversible mechanism in combination with cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PL biosynthesis. Thus liver nLD and cLD are both dynamic cellular organelles.