Lipid droplets formation and their effects on phosphatidylinositol level in yeasts

Abstract

Lipid droplets (LDs) are conserved specialized organelles that are surrounded by a single phospholipid layer, enclosing neutral lipids in form of triacylglycerol (TAG) and/or sterol ester. They are formed at the endoplasmic reticulum (ER), and stay connected to it in the yeast cell. These LDs mainly play major roles in lipid storage and homeostasis. Moreover, they have  several functions in the yeast cell including; protein degradation, protein glycosylation, response to ER stress, in addition to providing substrate for energy metabolism and for membrane synthesis. In general, TAG and phosphatidylinositol (PI) synthesis share the same precursor; phosphatidic acid (PA), which controls their level. By the actions of lipases, phosphatases and/or kinases; one can act as a precursor for another, thus explaining the reason of their inverse correlation. TAG lipolysis is catalyzed by TAG lipases producing fatty acids and diacylglycerol (DAG). The DAG produced from lipolysis is phosphorylated by diacylglycerol kinase (Dgk1) to form PA. On the other hand, PA is a cell signaling molecule and once increased, it upregulates cytidine diphosphate diacylglycerol (CDP-DAG) pathway for the PI synthesis. Major TAG lipases are mainly localized in LD, whereas minor amounts of them are localized in ER. Once DAG is produced inside the LD, it is transferred to the ER by inheritance cortical ER protein, Ice2, for further reactions. The TAG and PI levels are also controlled by transcriptional regulation in response to inositol and zinc. The aim of this study was to clarify how LDs regulate lipid homeostasis in the yeast cell, and particularly focuses on the balance between TAG and PI.