Abstract
Cytosolic lipid droplets were considered until recently to be rather inert particles of stored neutral lipid. Largely through proteomics is it now known that droplets are dynamic organelles and that they participate in several important metabolic reactions as well as trafficking and interorganellar communication. In this review, the role of droplets in metabolism in the yeast Saccharomyces cerevisiae, the fly Drosophila melanogaster, and several mammalian sources are discussed, particularly focusing on those reactions shared by these organisms. From proteomics and older work, it is clear that droplets are important for fatty acid and sterol biosynthesis, fatty acid activation, and lipolysis. However, many droplet-associated enzymes are predicted to span a membrane two or more times, which suggests either that droplet structure is more complex than the current model posits, or that there are tightly bound membranes, particularly derived from the endoplasmic reticulum, which account for the association of several of these proteins.
Highlights
Cytosolic lipid droplets were considered until recently to be rather inert particles of stored neutral lipid
There is general agreement that droplets are comprised of a core of neutral lipids, principally triglycerides and steryl esters, surrounded by a leaflet of phospholipids into which are embedded a specific subset of cellular proteins, the most abundant of which are members of the PAT family in animal cells [1]
This model is probably too simple; there is evidence from physical probes of droplets isolated from yeast mutants unable to synthesize triglycerides or steryl esters that these two molecular families are partially segregated within the core, with thin shells of steryl esters forming concentric hollow spheres around an inner core composed principally of triglycerides [2]
Summary
The first step in fatty acid synthesis is the generation of malonyl-CoA, catalyzed by acetyl-CoA carboxylase, the rate-limiting enzyme in the pathway. Fatty acids must be activated to CoA thioesters to be oxidized in the mitochondria and peroxisomes or added to glycerol or sphinganine to form triglycerides or sphingolipids, respectively Both acetylCoA carboxylase and acyl-CoA synthetases have been identified in several droplet proteomes (Table 1). Elongation of fatty acids beyond palmitate in mammals and perhaps in yeast [16] is promoted by elongase and desaturase enzymes localized in the ER, requiring NADPH. This source of reducing equivalents can be provided by cytochrome b5 reductase (Cyb5r) [20]. Generates acetyl-CoA Generates malonyl CoA Drosophila; early step in FA synthesis Drosophila Redox carrier in FA elongation and many others Many hydrophobic spans likely
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