Packaging of Fat: An Evolving Model of Lipid Droplet Assembly and Expansion
ABSTRACT Lipid droplets (LDs) are organelles found in most types of cells in the tissues of vertebrates, invertebrates, and plants, as well as in bacteria and yeast. They differ from other organelles in binding a unique complement of proteins and lacking an aqueous core but share aspects of protein trafficking with secretory membrane compartments. In this minireview, we focus on recent evidence supporting an endoplasmic reticulum origin for LD formation and discuss recent findings regarding LD maturation and fusion.
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- "In the late phase of adipocyte differentiation, PLIN2 expression gradually declines and is replaced by PLIN1 in mature adipocytes . PLIN2 primarily localizes to the surface of LDs as do PLIN1, whereas PLIN3 is stable in the cytoplasm and relocates to nascent LDs upon increased TAG synthesis . "
ABSTRACT: Cytosolic lipid droplets are dynamic lipid-storage organelles that play a crucial role as reservoirs of metabolic energy and membrane precursors. These organelles are present in virtually all cell types, from unicellular to pluricellular organisms. Despite similar structural organization, lipid droplets are heterogeneous in morphology, distribution and composition. The protein repertoire associated to lipid droplet controls the organelle dynamics. Distinct structural lipid droplet proteins are associated to specific lipolytic pathways. The role of these structural lipid droplet-associated proteins in the control of lipid droplet degradation and lipid store mobilization is discussed. The control of the strictly-regulated lipolysis in lipid-storing tissues is compared between mammals and plants. Differences in the cellular regulation of lipolysis between lipid-storing tissues and other cell types are also discussed. Copyright © 2015. Published by Elsevier B.V.Biochimie 07/2015; DOI:10.1016/j.biochi.2015.07.010 · 3.12 Impact Factor
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- "FAs can act as signalling molecules and can modulate major growth and metabolic pathways in the cell by acting as ligands for peroxisome proliferator-activated receptors (PPARs)   , by modulating liver X receptor (LXR) and sterol regulatory element-binding protein 1 (SREBP-1) transcription factor activities  , and even by binding to G protein coupledreceptors and activating growth and survival signalling cascades, such as the PI3K pathway  . However, FAs display a plethora of indirect signalling and metabolic effects as well, since they can be remodelled into membrane phospholipids, catabolised through mitochondrial FA oxidation or esterified into triacylglycerols (TAGs), which are stored in lipid droplets (LDs) in the cytosol of most cells, including cancer cells   . Several enzymes critical for the regulation of FA availability in the cell through synthesis, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and stearoyl-CoA desaturase-1 (SCD-1)  , and through lipolysis, such as monoacylglycerol lipase (MAGL)  , have been clearly associated with cancer. "
ABSTRACT: Secreted phospholipases A2 (sPLA2s) hydrolyse cell and lipoprotein phospholipid membranes to release free fatty acids and lysophospholipids, and can also bind to specific proteins. Several sPLA2s have been associated with various cancers, including prostate, colon, gastric, lung and breast cancers, yet, their role is controversial and seems to be dependent on the cancer type, the local microenvironment and the enzyme studied. There is strong evidence that the expression of some sPLA2s, most notably the group IIA, III and X enzymes, is dysregulated in various malignant tissues, where, as described in a number of in vitro and in vivo studies using mouse models and according to correlations between sPLA2 expression and patient survival, a particular enzyme may exert either a pro- or an anti-tumourigenic role. It is becoming clear that there are multiple, context-dependent mechanisms of action of sPLA2s in different cancers. First, the role of sPLA2s in cancer has traditionally been associated with their enzymatic activity and ability to participate in the release of potent biologically active lipid mediators, in particular arachidonic acid-derived eicosanoids, which promote tumourigenesis by stimulating cell proliferation and cell survival, by abrogating apoptosis and by increasing local inflammation and angiogenesis. Second, several biological effects of sPLA2s were found to be independent of sPLA2 enzymatic activity, arguing for a receptor-mediated mechanism of action. Finally, recent studies have implicated sPLA2s in the regulation of basal lipid metabolism, opening a new window to the understanding of the diverse roles of sPLA2s in cancer. In this short review, we highlight the newest findings on the biological roles of sPLA2s in cancer, with emphasis on their diverse mechanisms of action.Biochimie 10/2014; 107. DOI:10.1016/j.biochi.2014.09.023 · 3.12 Impact Factor
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- "In the past decade, LDs have emerged as heterogeneous organelles with great dynamics in size, abundance, and composition in regard to both proteins and lipids.60 Recent studies have provided more details on LD structure, biogenesis, function, and molecular regulation.3,13,15,61,62 Given the conservation among the basic mechanisms of control of lipid metabolism,63 studies in insects41 and other systems have been instrumental to the advancement of this field. "
ABSTRACT: The main cells of the adipose tissue of animals, adipocytes, are characterized by the presence of large cytosolic lipid droplets (LDs), which store triglyceride (TG) and cholesterol. However, most cells have LDs and the ability to store lipids. LDs have a well-known central role in storage and provision of fatty acids and cholesterol. However, the complexity of the regulation of lipid metabolism on the surface of the LDs is still a matter of intense study. Beyond this role, a number of recent studies have suggested that LDs have major functions in other cellular processes, such as protein storage and degradation, and infection and immunity. Thus, our perception of LDs, from simple globules of fat to highly dynamic organelles of unexpected complexity, has been radically transformed. Here we compiled some recent evidence supporting the emerging view that LDs act as platforms connecting a number of relevant metabolic and cellular functions.Lipid Insights 05/2014; 7:7-16. DOI:10.4137/LPI.S11128