Demonstrated and inferred metabolism associated with cytosolic lipid droplets

Abstract

The next layer of complexity is the functional inhomogeneity of droplets. Subsets of droplets within the same cells exist with different populations of PAT proteins, differentiating among different sizes, ages, and levels of metabolic activity ( 3,4 ). Perhaps most surprisingly, droplets may be comprised, at least in some cases, not of the layered core-phospholipid shell architecture at all but a knot of tightly woven endoplasmic reticulum (ER) surrounded by secreted neutral lipid, itself encased with a single leaflet. Such a model is based on electron microscopic thin sections ( 5 ), freeze fracture-immunogold evidence ( 6 ), immunohistochemical studies of ER luminal proteins within the droplet ( 7 ), and the identifi cation of these proteins, notably ER chaperones, in several proteomic studies. Although certainly, such a complex structure must obey physical laws governing aqueous interactions with hydrophobic lipids and artifacts in processing for electron microscopy do occur, it may be best at present to keep an open mind and consider that droplets may not have the same structure among tissues and that they may take multiple physical forms in rapid order as they dynamically perform their functions.What are these functions? The most obvious one is lipid metabolism, namely the biogenesis and breakdown of the neutral lipids contained within the droplet. Although this conclusion predates proteomic studies ( 8 ), these recent studies have revealed the breadth and conservation of metabolic reactions that occur at or near the droplet surface, the subject of this review. Moreover, proteomics has demonstrated the surprising fact that droplets are likely to be very active in organellar communication because they are replete in rab proteins and other traffi cking molecules. Our knowledge from proteomic studies of droplet 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 traffi cking and interorganellar communication. In this review, the role of droplets in metabolism in the yeast Saccharomyces cerevisiae , the fl y 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. Cytosolic lipid droplets, originally thought to be simply coalesced neutral lipids waiting for lipolysis at metabolic demand, are now known to be considerably more...

A squalene synthase protein degradation method for improved sesquiterpene production in Saccharomyces cerevisiae

“…Consistent with this localisation pattern, several other enzymes from ergosterol synthetic pathway, including Erg1p, Erg7p, and Erg27p, are also co-located in ER and LDs (Goodman, 2009;Leber et al, 1998). As observed previously (Llopis et al, 1998;Mateus and Avery, 2000), un-tagged GFP is located in both cytosol and nucleus (Supplementary Materials: Fig.…”

Not Just Fat: The Structure and Function of the Lipid Droplet

“…Enzymes involved in various lipid metabolic pathways including fatty acid and steroid synthesis and fatty acid activation are recovered in LD and membrane fraction (Goodman 2009 that some metabolic reactions occur in LDs, but many of those enzyme molecules are thought to be multispanning membrane proteins and are not likely to reside in the phospholipid monolayer of the LD surface. A simple assumption is that the enzymes are in the ER membrane adjacent to LDs and are recovered in the LD fraction as contaminants.…”

“…A simple assumption is that the enzymes are in the ER membrane adjacent to LDs and are recovered in the LD fraction as contaminants. However, the activity of some enzymes is different depending on the existing fraction (Goodman 2009), suggesting that the dichotomous partitioning has physiological relevance. It is possible, for example, that the ER membrane is separated into the lipid ester-poor and -rich domains, and that the latter is recovered in the LD fraction because of its relatively high buoyancy.…”

Controlling Lipid Fluxes at Glycerol-3-phosphate Acyltransferase Step in Yeast

“…This implies LPs are not just a static storage compartment but a dynamic structure that actively participates in maintaining lipid homeostasis (1)(2)(3). LPs have a signature proteome and lipidome that responds to environmental and nutritional conditions of cells (4,5).…”