Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains

Kassan, Adam; Herms, Albert; Fernández-Vidal, Andrea; Bosch, Marta; Schieber, Nicole L.; Reddy, Babu J.N.; Fajardo, Alba; Gelabert-Baldrich, Mariona; Tebar, Francesc; Enrich, Carlos; Gross, Steven P.; Parton, Robert G.; Pol, Albert

doi:10.1083/jcb.201305142

Cited by 264 publications

(333 citation statements)

References 63 publications

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“…Instead of a dynamic alteration of phospholipids or surface tension for LD budding, the ER may simply display regions or microdomains (Kassan et al, 2013) enriched with particular phospholipids or that transiently have specific surface tensions. Such segregation could occur between the smooth and rough ER, nuclear and peripheral ER, and ER tubules and sheets (Lagace and Ridgway, 2013).…”

Section: Discussionmentioning

confidence: 99%

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

et al. 2017

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SUMMARYCells convert excess energy into neutral lipids that are made in the endoplasmic reticulum (ER) bilayer. The lipids are then packaged into spherical or budded lipid droplets (LDs) covered by a phospholipid monolayer containing proteins. LDs play a key role in cellular energy metabolism and homeostasis. A key unanswered question in the life of LDs is how they bud off from the ER. Here, we tackle this question by studying the budding of artificial LDs from model membranes. We find that the bilayer phospholipid composition and surface tension are key parameters of LD budding. Phospholipids have differential LD budding aptitudes, and those inducing budding decrease the bilayer tension. We observe that decreasing tension favors the egress of neutral lipids from the bilayer and LD budding. In cells, budding conditions favor the formation of small LDs. Our discovery reveals the importance of altering ER physical chemistry for controlled cellular LD formation.

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Section: Discussionmentioning

confidence: 99%

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

et al. 2017

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“…LDs and ER could be directly connected by a continuity in their membranes [24,25], which would allow the transfer of lipids from the ER to support LD growth. In addition, these LD-ER connections could promote LD growth by facilitating the diffusion of lipogenic enzymes from the ER to increase in situ lipid synthesis [24,26].…”

Section: The Er In Ld Biogenesis and Growthmentioning

confidence: 99%

Lipid droplet growth: regulation of a dynamic organelle

Barneda

Christian

2017

Current Opinion in Cell Biology

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Intracellular lipid droplets (LDs) are remarkably dynamic and complex organelles that enact regulated storage and release of lipids to fulfil their fundamental roles in energy metabolism, membrane synthesis and provision of lipid-derived signaling molecules.Although small LDs are observed in all types of eukaryotic cells, it is adipocytes that present the widest range of sizes up to the massive unilocular droplet of a white adipocyte. Our knowledge of the proteins and associated processes that control LD dynamics is improving. The dynamic expression of LD-associated proteins is vital for controlling LD biology and is most apparent during adipocyte differentiation. Recent findings on the molecular mechanisms of lipid droplet enlargement reveal the importance of distinct functional groups of proteins and phospholipids.Highlights (max 5 points 85 characters each) Lipid droplet fusion involves major changes in the LD membrane components.Phosphatidic Acid is a key regulator of LD dynamics.Adipocyte differentiation invokes profound regulation of lipid droplet proteins.Transitions between white and BRITE adipocytes require lipid droplet remodelling.

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“…Freeze fracture experiments have revealed that the ER membrane is continuous with the surface layer of lipid droplets or that it encloses lipid droplets tightly (Blanchette-Mackie et al, 1995;Robenek et al, 2006). Functional studies have indicated that the activation of fatty acids and their incorporation into triacylglycerol occurs at specific ER microdomains from where lipid droplets grow (Kassan et al, 2013;Xu et al, 2012b). The contact sites between the ER and lipid droplets have also been characterized and shown to be stabilized by the seipin complex, which acts as a diffusion barrier between the two compartments (Grippa et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Mature lipid droplets are accessible to ER luminal proteins

Mishra

Khaddaj

Cottier

et al. 2016

Journal of Cell Science

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Lipid droplets are found in most organisms where they serve to store energy in the form of neutral lipids. They are formed at the endoplasmic reticulum (ER) membrane where the neutral-lipidsynthesizing enzymes are located. Recent results indicate that lipid droplets remain functionally connected to the ER membrane in yeast and mammalian cells to allow the exchange of both lipids and integral membrane proteins between the two compartments. The precise nature of the interface between the ER membrane and lipid droplets, however, is still ill-defined. Here, we probe the topology of lipid droplet biogenesis by artificially targeting proteins that have high affinity for lipid droplets to inside the luminal compartment of the ER. Unexpectedly, these proteins still localize to lipid droplets in both yeast and mammalian cells, indicating that lipid droplets are accessible from within the ER lumen. These data are consistent with a model in which lipid droplets form a specialized domain in the ER membrane that is accessible from both the cytosolic and the ER luminal side.

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Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains

Abstract: Acyl-CoA synthetase 3 is recruited early to lipid droplet assembly sites on the ER, where it is required for efficient lipid droplet nucleation and lipid storage.

Cited by 264 publications

References 63 publications

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

Lipid droplet growth: regulation of a dynamic organelle

Mature lipid droplets are accessible to ER luminal proteins

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