Interactions of Lipid Droplets with the Intracellular Transport Machinery

Abstract

Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and lipid droplets. There is a large recent body of work on these organelles, which have resulted in the introduction of new paradigms regarding the roles of membrane trafficking organelles. In this review, we discuss the roles of membrane trafficking in the life cycle of lipid droplets. This includes the complementary roles of lipid phase separation and proteins in the biogenesis of lipid droplets from endoplasmic reticulum (ER) membranes, and the attachment of mature lipid droplets to membranes by lipidic bridges and by more conventional protein tethers. We also discuss the catabolism of neutral lipids, which in part results from the interaction of lipid droplets with cytosolic molecules, but with important roles for both macroautophagy and microautophagy. Finally, we address their eventual demise, which involves interactions with the autophagocytotic machinery. We pay particular attention to the roles of small GTPases, particularly Rab18, in these processes.

Comprehensive and Quantitative Analysis of the Changes in Proteomic and Phosphoproteomic Profiles during Stimulation and Repression of Steroidogenesis in MA-10 Leydig Cells

“…Vesicle trafficking is an important process for steroidogenesis. For instance, the life cycle of lipid droplets, which are a source of cholesterol substrate for steroid hormones [ 21 ], involves intracellular trafficking (reviewed in [ 22 ]). The significant and rapid changes in Dymeclin protein levels in response to Fsk and Fsk+AICAR suggest that Dymeclin might play an active role in hormone-regulated steroidogenesis in Leydig cells.…”

Exploiting Directed Self-Assembly and Disassembly for off-to-on Fluorescence Responsive Live Cell Imaging

“…42 In eukaryotes cells, the site of biogenesis of LDs is the phospholipid bilayer of the ER. 38,[43][44] As triacylglycerol's are biosynthesised within the ER they accumulate within its bilayer leading first to the budding and then monolayer enclosing of a LD. 38 This phospholipid monolayer provides structural integrity and stability to the LD in the cell.…”

The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity

“…In experimental models of NAFLD, cholesterol is more associated with large than small LDs in hepatocytes [ 15 , 16 ]. The size of LDs after their formation depends on very complex mechanisms including their catabolism through lipolysis and different types of lipophagy, their eventual fusion and, probably, also lipid synthesis on their surface [ 10 , 17 , 18 , 19 , 20 ]. Patatin-like phospholipase domain protein 3 (PNPLA3) is one lipolytic enzyme in hepatocytes located on large lipid droplets and several studies have shown that the PNPLA3 rs738409 (I148M) variant is powerfully linked to hepatic damage in NAFLD, at different levels such as steatosis, necroinflammation and fibrosis [ 21 , 22 ].…”

“…The percentage of steatotic hepatocytes in the liver and the size of LDs in each steatotic hepatocyte are determined not only by the imbalance between lipid supply and utilization/secretion but also by the amount/activity of regulatory surface proteins, including PNPLA3, and of lysosomal enzymes, which can differ in the hepatocytes of the same liver [ 17 , 20 , 21 , 27 , 28 , 29 , 30 ]. As a result, in the same human liver, heterogeneous populations of hepatocytes with and without steatosis can coexist, and, among the former, sometimes the size of the LDs is uniform, or some hepatocytes may contain large and others small LDs.…”