Yeast lipid droplet dynamics are coupled to sphingolipid biosynthesis via Tsc3p

This is the authors' abstract. We don't add key points for this paper.

Abstract Regulation of lipid metabolism is pivotal for living cells to maintain the balance between energy production and membrane component assembly. Fatty acids can be stored as triacylglycerols in lipid droplets (LD) or accumulate in various subcellular compartments as diacylglycerols or sphingolipids, which may exert deleterious effects and associate with metabolic diseases. At present, the mechanisms maintaining the balance of neutral lipid synthesis and consumption remain largely unknown. Thus, this study aimed to identify regulators of LD dynamics in yeast. Based on flow cytometry we assess LD consumption in candidates involved in first steps of sphingolipid synthesis. We found that the Tsc3p deletion strain (tsc3Δ) displayed a decrease in LD consumption, which was reversed by adding phytosphingosine. Assessment of lipidomic profiles revealed decreased ceramide level in tsc3Δ cells. In addition, we determined the subcellular localization of Tsc3p and analogous human small subunits of the serine palmitoyltransferase to the endoplasmic reticulum and that ssSPTb rescues the LD consumption defect in tsc3Δ cells. In conclusion, our data show that tsc3Δ impairs LD breakdown accompanied by low cellular sphingolipid level which lead to suggestion that Tsc3p is required for efficient sphingolipid biosynthesis for maintaining cellular lipid homeostasis.