SPHINGOSINE KINASE 2 AS REGULATOR OF LIPID DROPLETS BIOGENESIS

SANTACREU, BJ; OTERO, D; ROMERO, DJ; STERIN - SPEZIALE, NB; TARALLO, E; FAVALE, NO

Salta

Congreso; 55th Annual Meeting Argentine Society for Biochemistry and Molceular Biology; 2019

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Sphingolipids (SLP) participate in several different, even opposite, cellular processes. We have described their participation in the cellular differentiation of renal collecting tubule. We have observed that the levels of sphingosine 1 phosphate (S1P) regulate the levels of the other SLPby inhibition of enzymes involved in de novo SLP synthesis. In this way, S1P emerges as a general regulator of the level of sphingolipids, which adapts the SLP levels to the cellular fate. However, less it is known about the interrelation of S1P with phospholipids, triglycerides or other lipids.In this work, we study the importance of S1P in relation to the dynamics of lipid droplets. We found that the activity of sphingosine kinase 2 (SphK2), one isoform of the enzyme that synthetizes S1P, is necessary for the formation of lipid droplet (LD). SphK2 activity modification by pharmacological, siRNA and CRISPR/cas9 strategies produced a decrease in LD size and number. This observation was accompanied by a decrease in triglycerides and was not reversed by S1P receptor antagonists or inhibitors of the de novo SLP synthesis. Additionally, by using bioinformatic analysis of the RNA-seq database, we found that SphK2 knockout mice present an alteration in the mRNA levels of the key enzymes of triglyceride synthesis. On the other hand, we found that SphK2 is located on the surface of lipid droplets by fluorescence microscopy. These results show that the SphK2/S1P pathway could play a central role in the regulation of the complex lipid metabolism, regulating, in this case, the biogenesis of lipid droplets.