Lipid droplets as dynamic organelles connecting storage and efflux of lipids

Olofsson, Sven-Olof; Boström, Pontus; Andersson, Linda; Rutberg, Mikael; Perman, Jeanna; Borén, Jan

doi:10.1016/j.bbalip.2008.08.001

Cited by 220 publications

(163 citation statements)

References 154 publications

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“…3A). TAGs and cholesterol esters are known to be stored intracellularly in lipid droplets (23)(24)(25)(26). Immunofluorescence for adipocyte differentiation-related protein (ADRP), a lipid droplet marker (27), showed an increase in lipid droplets in both the progenitor layers and NL of E13.5 SQS-cKO brain tissue compared with control, which was particularly striking for the DiE (Fig.…”

Section: Lipid Droplets Containing Triacylglycerides With Unsaturatedmentioning

confidence: 88%

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis

Saito

Dubreuil

Arai

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5-E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1-independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis.lipid droplets ͉ mass spectrometry ͉ neuroepithelial cells ͉ neurogenesis ͉ radial glia

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Section: Lipid Droplets Containing Triacylglycerides With Unsaturatedmentioning

confidence: 88%

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis

Saito

Dubreuil

Arai

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Assembly of VLDL starts with the cotranslational lipidation of apoB-100 by microsomal triglyceride transfer protein delivering lipids from cytosolic lipid droplets into the endoplasmic reticulum lumen (32,33). The resulting primordial lipoprotein is further lipidated into a triglyceride-poor form of VLDL that is released from the endoplasmic reticulum at distinct exit sites and transported to the Golgi apparatus.…”

Section: Flagmentioning

confidence: 99%

Biochemical and Morphological Properties of Hepatitis C Virus Particles and Determination of Their Lipidome

Merz

Long

Hiet

et al. 2011

Journal of Biological Chemistry

312

355

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A hallmark of hepatitis C virus (HCV) particles is their association with host cell lipids, most notably lipoprotein components. It is thought that this property accounts for the low density of virus particles and their large heterogeneity. However, the composition of infectious virions and their biochemical and morphological properties are largely unknown. We developed a system in which the envelope glycoprotein E2 was Nterminally tagged with a FLAG epitope. This virus, designated Jc1E2 FLAG , produced infectivity titers to wild type levels and allowed affinity purification of virus particles that were analyzed for their protein and lipid composition. By using mass spectrometry, we found the lipid composition of Jc1E2 FLAG particles to resemble the one very low-and low density-lipoprotein with cholesteryl esters accounting for almost half of the total HCV lipids. Thus, HCV particles possess a unique lipid composition that is very distinct from all other viruses analyzed so far and from the human liver cells in which HCV was produced. By electron microscopy (EM), we found purified Jc1E2 FLAG particles to be heterogeneous, mostly spherical structures, with an average diameter of about 73 nm. Importantly, the majority of E2-containing particles also contained apoE on their surface as assessed by immuno-EM. Taken together, we describe a rapid and efficient system for the production of large quantities of affinity-purified HCV allowing a comprehensive analysis of the infectious virion, including the determination of its lipid composition.

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“…Oxidative injury to the phospholipid monolayer around the droplets, altered expression of PAT in NASH and the interaction of droplets with cytoskeletal elements suggests that dysfunction of these organelles may be central to NASH pathogenesis [41][42][43][44][45][46]. Potentially important factors include altered droplet fusion and interaction with the cytoskeleton [47,48]. Using conventional fixation techniques and protocol morphometry, we recently demonstrated an association between the accumulation of small-to-medium sized lipid droplets, cellular keratin depletion, MDBs and cellular ballooning, suggesting impaired fat droplet metabolism in NASH [31].…”

Section: Fat Dropletsmentioning

confidence: 99%