Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites

Gong, Jingyi; Sun, Zhiqi; Wu, Lizhen; Xu, Wenyi; Schieber, Nicole L.; Xu, Duanyi; Shui, Guanghou; Yang, Hongyuan; Parton, Robert G.; Li, Peng

doi:10.1083/jcb.201104142

Cited by 281 publications

(328 citation statements)

References 30 publications

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“…Second, OBs would remain tethered to the ER, filling with neutral lipids until an optimal size is reached, allowing their release into the cytosol. Third, large OBs could also result from the fusion or coalescence of smaller ones (Gong et al, 2011;Ariotti et al, 2012). These different mechanisms may depend on the type of LD, on cell type, and on the neutral lipids accumulated (Cheng et al, 2009;Thiam et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Recent data suggest that this view of OBs is probably too simple to explain OB fusions and fragmentations (fissions), organelle interactions, or the transport needed for the dynamic variations of V OB Thiam et al, 2013). In animals, the net transfer of storage lipids from smaller LDs to larger ones without redistribution of LD proteins from donor to acceptor has been shown (Gong et al, 2011). Also, the synthesis of TAGs can be directly coupled with the formation of LDs that share common features with plant OBs, thus indicating a growth process independent of fusions with existing LDs or with the ER .…”

Section: Oleosins Ole1 Ole2 and Ole4 Have Different Rolesmentioning

confidence: 99%

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Specialization of Oleosins in Oil Body Dynamics during Seed Development in Arabidopsis Seeds

et al. 2014

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Oil bodies (OBs) are seed-specific lipid storage organelles that allow the accumulation of neutral lipids that sustain plantlet development after the onset of germination. OBs are covered with specific proteins embedded in a single layer of phospholipids. Using fluorescent dyes and confocal microscopy, we monitored the dynamics of OBs in living Arabidopsis (Arabidopsis thaliana) embryos at different stages of development. Analyses were carried out with different genotypes: the wild type and three mutants affected in the accumulation of various oleosins (OLE1, OLE2, and OLE4), three major OB proteins. Image acquisition was followed by a detailed statistical analysis of OB size and distribution during seed development in the four dimensions (x, y, z, and t). Our results indicate that OB size increases sharply during seed maturation, in part by OB fusion, and then decreases until the end of the maturation process. In single, double, and triple mutant backgrounds, the size and spatial distribution of OBs are modified, affecting in turn the total lipid content, which suggests that the oleosins studied have specific functions in the dynamics of lipid accumulation.The seed is a complex, specific structure that allows a quiescent plant embryo to cope with unfavorable germinating conditions and also permits dissemination of the species. To achieve these functions, seeds accumulate reserve compounds that will ensure the survival of the embryo and fuel the growth of the plantlet upon germination. Accumulation of lipids occurs in many eukaryotic cells and is a rather common means of storing carbon and energy. Lipid droplets (LDs) can be found in all eukaryotes, such as yeast (Saccharomyces cerevisiae;

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Section: Discussionmentioning

confidence: 99%

Section: Oleosins Ole1 Ole2 and Ole4 Have Different Rolesmentioning

confidence: 99%

Specialization of Oleosins in Oil Body Dynamics during Seed Development in Arabidopsis Seeds

et al. 2014

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“…Both CIDEA and CIDEC catalyse a slow fusion mechanism in which a donor LD transfers its content to a larger LD in a process driven by their internal pressure gradient [34]. CIDE proteins stabilize LD pairs by the formation of trans homodimers at the LD-LD contact site [19, 34,35], where they facilitate the transport of neutral lipids through the phospholipid monolayer. The lipid transfer step requires the presence of a cationic amphipathic helix, which by interacting with PA could interfere with the phospholipid barrier to increase its permeability to TAG [19].…”

Section: Ld-ld Fusionmentioning

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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“…Fat-specific protein 27 (Fsp27/Cidec), a lipid droplet-associated protein in adipocytes, is mainly localized at the contact point of lipid droplets and promotes atypical lipid droplet fusion and formation of unilocular lipid droplets in adipocytes (44). Upon examination, the levels of Fsp27 protein were increased by PKA activation (Fig.…”

Section: Pka Subunit Stoichiometrymentioning

confidence: 99%

Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis elegans and Mammalian Adipocytes

Lee

Han

Kong

et al. 2016

Journal of Biological Chemistry

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Protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent protein kinase composed of catalytic and regulatory subunits and involved in various physiological phenomena, including lipid metabolism. Here we demonstrated that the stoichiometric balance between catalytic and regulatory subunits is crucial for maintaining basal PKA activity and lipid homeostasis. To uncover the potential roles of each PKA subunit, Caenorhabditis elegans was used to investigate the effects of PKA subunit deficiency. In worms, suppression of PKA via RNAi resulted in severe phenotypes, including shortened life span, decreased egg laying, reduced locomotion, and altered lipid distribution. Similarly, in mammalian adipocytes, suppression of PKA regulatory subunits RI␣ and RII␤ via siRNAs potently stimulated PKA activity, leading to potentiated lipolysis without increasing cAMP levels. Nevertheless, insulin exerted anti-lipolytic effects and restored lipid droplet integrity by antagonizing PKA action. Together, these data implicate the importance of subunit stoichiometry as another regulatory mechanism of PKA activity and lipid metabolism.Protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent serine/threonine kinase that mediates various cellular responses, including lipolysis. Since its discovery in the 1950s (1-4), the cAMP-PKA system has become one of the best understood signaling pathways in terms of biochemical properties. PKA is composed of catalytic subunits and cAMP-binding regulatory subunits (5). In the absence of cAMP stimulation, PKA forms an inactive tetramer composed of four subunits with two regulatory and two catalytic subunits. Upon nutritional deprivation or hormonal stimulation, activated adenylyl cyclase produces cAMP from ATP. Then, the regulatory subunit of PKA binds cAMP, causing a conformational change that decreases its affinity for catalytic subunits by ϳ10 4 -fold and leads to the release of active catalytic subunits to phosphorylate target proteins (6, 7).PKA has a wide range of substrates that regulate a number of physiological processes. To date, several hundred PKA target proteins have been identified, and yet new PKA substrates are continually being reported (8, 9). In mammalian adipocytes, numerous studies over the last 40 years have revealed that the cAMP-PKA axis forms a critical node in the regulation of lipolysis. For instance, major components of lipolytic pathways, including hormone-sensitive lipase (Hsl) 2 and perilipin 1 (Plin1), are direct targets of PKA (10, 11). Recently, adipose triglyceride lipase (Atgl) was also reported to be a target of PKA (12, 13). Upon receiving activation signals from molecules such as catecholamine and glucagon, activated PKA phosphorylates Plin1 and HSL to promote the recruitment of HSL to lipid droplets (14, 15). In addition, phosphorylated Plin1 releases comparative gene identification-58 (CGI-58; Abhd5), a coactivator of Atgl, to mediate lipolysis upon PKA activation (16 -20). On the contrary, insulin can activate phosphodiesterase 3B (Pde3b) and reduce cAMP levels (1...

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Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites

Abstract: The lipid droplet–associated protein Fsp27 mediates lipid droplet growth by promoting directional lipid transfer from smaller to larger lipid droplets.

Cited by 281 publications

References 30 publications

Specialization of Oleosins in Oil Body Dynamics during Seed Development in Arabidopsis Seeds

Specialization of Oleosins in Oil Body Dynamics during Seed Development in Arabidopsis Seeds

Lipid droplet growth: regulation of a dynamic organelle

Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis elegans and Mammalian Adipocytes

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