Morphologically and Functionally Distinct Lipid Droplet Subpopulations.

Published on Jul 8, 2016in Scientific Reports4.38
· DOI :10.1038/SREP29539
Shuyan Zhang14
Estimated H-index: 14
(CAS: Chinese Academy of Sciences),
Yang Wang21
Estimated H-index: 21
(CAS: Chinese Academy of Sciences)
+ 7 AuthorsPingsheng Liu51
Estimated H-index: 51
(CAS: Chinese Academy of Sciences)
Sources
Abstract
Lipid droplet (LD), a multi-functional organelle, is often found to associate with other cellular membranous structures and vary in size in a given cell, which may be related to their functional diversity. Here we established a method to separate LD subpopulations from isolated CHO K2 LDs into three different size categories. The subpopulation with smallest LDs was nearly free of ER and other membranous structures while those with larger LDs contained intact ER. These distinct subpopulations of LDs differed in their protein composition and ability to recruit proteins. This method was also applicable to LDs obtained from other sources, such as Huh7 cells, mouse liver and brown adipose tissue, et al. We developed an in vitro assay requiring only isolated LDs, Coenzyme A, and ATP to drive lipid synthesis. The LD subpopulation nearly depleted of ER was able to incorporate fatty acids into triacylglycerol and phospholipids. Together, our data demonstrate that LDs in a given cell are heterogeneous in size and function, and suggest that LDs are one of cellular lipid synthetic organelles.
📖 Papers frequently viewed together
200949.96Nature
9 Authors (Rajat Singh, ..., Mark J. Czaja)
16 Authors (Huajin Wang)
References59
Newest
#1Jinhai Yu (CAS: Chinese Academy of Sciences)H-Index: 15
#2Shuyan Zhang (CAS: Chinese Academy of Sciences)H-Index: 14
Last. Pingsheng Liu (CAS: Chinese Academy of Sciences)H-Index: 51
view all 11 authors...
Abstract Brown adipose tissue (BAT) maintains animal body temperature by non-shivering thermogenesis, which is through uncoupling protein 1 (UCP1) that uncouples oxidative phosphorylation and utilizes β-oxidation of fatty acids released from triacylglycerol (TAG) in lipid droplets (LDs). Increasing BAT activity and “browning” other tissues such as white adipose tissue (WAT) can enhance the expenditure of excess stored energy, and in turn reduce prevalence of metabolic diseases. Although many stu...
Source
#1Zhiwei Zhu (DICP: Dalian Institute of Chemical Physics)H-Index: 15
#2Yunfeng DingH-Index: 10
Last. Zongbao K. Zhao (DICP: Dalian Institute of Chemical Physics)H-Index: 56
view all 14 authors...
Lipid droplets (LDs) are ubiquitous organelles that serve as a neutral lipid reservoir and a hub for lipid metabolism. Manipulating LD formation, evolution, and mobilization in oleaginous species may lead to the production of fatty acid-derived biofuels and chemicals. However, key factors regulating LD dynamics remain poorly characterized. Here we purified the LDs and identified LD-associated proteins from cells of the lipid-producing yeast Rhodosporidium toruloides cultured under nutrient-rich,...
Source
#1Wen Su (PKU: Peking University)H-Index: 13
#2Yang Wang (CAS: Chinese Academy of Sciences)H-Index: 21
Last. Youfei Guan (PKU: Peking University)H-Index: 58
view all 18 authors...
Nonalcoholic fatty liver disease (NAFLD) is characterized by a massive accumulation of lipid droplets (LDs). The aim of this study was to determine the function of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), one of our newly identified LD-associated proteins in human subjects with normal liver histology and simple steatosis, in NAFLD development. LDs were isolated from 21 human liver biopsies, including 9 cases with normal liver histology (group 1) and 12 cases with simple steatosis (group ...
Source
#1Daniel F. Markgraf (HHMI: Howard Hughes Medical Institute)H-Index: 16
#2Robin W. Klemm (HHMI: Howard Hughes Medical Institute)H-Index: 17
Last. Tom A. Rapoport (HHMI: Howard Hughes Medical Institute)H-Index: 125
view all 6 authors...
Summary Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae , LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ...
Source
Lipid droplets (LDs) store metabolic energy and membrane lipid precursors. With excess metabolic energy, cells synthesize triacylglycerol (TG) and form LDs that grow dramatically. It is unclear how TG synthesis relates to LD formation and growth. Here, we identify two LD subpopulations: smaller LDs of relatively constant size, and LDs that grow larger. The latter population contains isoenzymes for each step of TG synthesis. Glycerol-3-phosphate acyltransferase 4 (GPAT4), which catalyzes the firs...
Source
#1Yunfeng Ding (CAS: Chinese Academy of Sciences)H-Index: 10
#2Shuyan Zhang (CAS: Chinese Academy of Sciences)H-Index: 14
Last. Pingsheng LiuH-Index: 51
view all 14 authors...
The lipid droplet (LD) is a cell organelle that has been linked to human metabolic syndromes and that can be exploited for the development of biofuels. The isolation of LDs is crucial for carrying out morphological and biochemical studies of this organelle. In the past two decades, LDs have been isolated from several organisms and investigated by microscopy, proteomics and lipidomics. However, these studies need to be extended to more model organisms, as well as to more animal tissues. Thus, a s...
Source
#1Peng Zhang (CAS: Chinese Academy of Sciences)H-Index: 8
#2Huimin Na (CAS: Chinese Academy of Sciences)H-Index: 10
Last. Pingsheng Liu (CAS: Chinese Academy of Sciences)H-Index: 51
view all 16 authors...
Lipid droplets (LDs) are a neutral lipid storage organelle that is conserved across almost all species. Many metabolic syndromes are directly linked to the over-storage of neutral lipids in LDs. The study of LDs in Caenorhabditis elegans (C. elegans) has been difficult because of the lack of specific LD marker proteins. Here we report the purification and proteomic analysis of C. elegans lipid droplets for the first time. We identified 306 proteins, 63% of these proteins were previously known to...
Source
#1Denis J. Murphy (University of South Wales)H-Index: 57
During the past decade, there has been a paradigm shift in our understanding of the roles of intracellular lipid droplets (LDs). New genetic, biochemical and imaging technologies have underpinned these advances, which are revealing much new information about these dynamic organelles. This review takes a comparative approach by examining recent work on LDs across the whole range of biological organisms from archaea and bacteria, through yeast and Drosophila to mammals, including humans. LDs proba...
Source
#1Varman T. Samuel (Yale University)H-Index: 59
#2Gerald I. Shulman (Yale University)H-Index: 183
Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway, and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, these cellular changes m...
Source
#1Yunfeng Ding (CAS: Chinese Academy of Sciences)H-Index: 10
#2Li Yang (CAS: Chinese Academy of Sciences)H-Index: 2
Last. Pingsheng LiuH-Index: 51
view all 16 authors...
Lipid droplets (LDs) are intracellular organelles with neutral lipid cores surrounded by a phospholipid monolayer and coated with various proteins (1–3). LDs have been found in almost all eukaryotic organisms from yeast to mammals (4). They interact with other cellular organelles (5–8), and their dynamics is closely related to the progression of metabolic diseases, such as obesity, fatty liver, type 2 diabetes mellitus, and atherosclerosis (9). Recent studies have also shown that LDs are involve...
Source
Cited By51
Newest
#1Rebekah Rakotonirina-Ricquebourg (IBMC: Instituto de Biologia Molecular e Celular)
#2Vítor Costa (IBMC: Instituto de Biologia Molecular e Celular)H-Index: 25
Last. Vitor Hugo Teixeira (University of Porto)H-Index: 18
view all 3 authors...
Lipid droplets (LDs) are ubiquitous organelles that play crucial roles in response to physiological and environmental cues. The identification of several neutral lipid synthesizing and regulatory protein complexes have propelled significant advance on the mechanisms of LD biogenesis in the endoplasmic reticulum (ER). Increasing evidence suggests that distinct proteins and regulatory factors, which localize to membrane contact sites (MCS), are involved not only in interorganellar lipid exchange a...
Source
#1Engui Zhao (HIT: Harbin Institute of Technology)H-Index: 2
Lipid droplet (LD) is a dynamic organelle responsible for lipid storage and metabolism, which plays important roles in maintaining lipid homeostasis. However, limited strategies are available for t...
Source
Last. Chii-Shiarng Chen (NDHU: National Dong Hwa University)H-Index: 23
view all 4 authors...
Intracellular lipid body (LB) biogenesis depends on the symbiosis between coral hosts and their Symbiodinaceae. Therefore, understanding the mechanism(s) behind LB biosynthesis in corals can portentially elucide the drivers of cellular regulation during endosymbiosis. This study assessed LB formation in the gastrodermal tissue layer of the hermatypic coral Euphyllia glabrescens. Diel rhythmicity in LB size and distribution was observed; solar irradiation onset at sunrise initiated an increase in...
Source
One of the characteristic features of metastatic breast cancer is increased cellular storage of neutral lipid in cytoplasmic lipid droplets (CLDs). CLD accumulation is associated with increased cancer aggressiveness, suggesting CLDs contribute to metastasis. However, how CLDs contribute to metastasis is not clear. CLDs are composed of a neutral lipid core, a phospholipid monolayer, and associated proteins. Proteins that associate with CLDs regulate both cellular and CLD metabolism; however, the ...
Source
#6Shau Ku Huang (NIH: National Institutes of Health)
Club cells are critical in maintaining airway integrity via, in part, secretion of immunomodulatory Club cell 10 kd protein (CC10) and xenobiotic detoxification. Aryl hydrocarbon receptor (AhR) is important in xenobiotic metabolism, but its role in Club cell function is unclear. To this end, an AhR ligand, 6-formylindolo[3,2-b]carbazole (FICZ, 10 nM) was found to induce, in a ligand and AhR-dependent manner, endoplasmic reticulum stress, phospholipid remodeling, free fatty acid and triglyceride ...
Source
#1Federica RoccioH-Index: 3
#2Aurore Claude-Taupin (University of Paris)H-Index: 3
Last. Nicolas Dupont (University of Paris)H-Index: 17
view all 6 authors...
Source
#1Silke Nuber (Brigham and Women's Hospital)H-Index: 5
#2Alice Y Nam (Brigham and Women's Hospital)H-Index: 2
Last. Dennis J. Selkoe (Brigham and Women's Hospital)H-Index: 194
view all 16 authors...
Objective Parkinson's disease (PD) has useful symptomatic treatments that do not slow the neurodegenerative process, and no significant disease-modifying treatments are approved. A key therapeutic target in PD is α-synuclein (αS), which is both genetically implicated and accumulates in Lewy bodies rich in vesicles and other lipid membranes. Reestablishing αS homeostasis is a central goal in PD. Based on previous lipidomic analyses, we conducted a mouse trial of a stearoyl-CoA desaturase (SCD) in...
Source
#1Liujuan Cui (CAS: Chinese Academy of Sciences)H-Index: 5
#2Pingsheng Liu (CAS: Chinese Academy of Sciences)H-Index: 51
Lipid droplets (LDs) and mitochondria are essential organelles involved in cellular lipid metabolism and energy homeostasis. Accumulated studies have revealed that the physical contact between these two organelles is important for their functions. Current understanding of the contact between cellular organelles is highly dynamic, fitting a "kiss-and-run" model. The same pattern of contact between LDs and mitochondria has been reported and several proteins are found to mediate this contact, such ...
Source
#1Kessiri Kongmanas (MU: Mahidol University)H-Index: 9
#2Nuntaya Punyadee (MU: Mahidol University)H-Index: 5
Last. Panisadee Avirutnan (MU: Mahidol University)H-Index: 15
view all 13 authors...
Suitable cell models are essential to advance our understanding of the pathogenesis of liver diseases and the development of therapeutic strategies. Primary human hepatocytes (PHHs), the most ideal hepatic model, are commercially available, but they are expensive and vary from lot-to-lot which confounds their utility. We have recently developed an immortalized hepatocyte-like cell line (imHC) from human mesenchymal stem cells, and tested it for use as a substitute model for hepatotropic infectio...
Source
#1Florian Geltinger (University of Salzburg)H-Index: 4
#2Lukas Schartel (University of Salzburg)H-Index: 1
Last. Mark Rinnerthaler (University of Salzburg)H-Index: 23
view all 7 authors...
Lipid droplets (LDs) were considered as a mere lipid storage organelle for a long time. Recent evidence suggests that LDs are in fact distinct and dynamic organelles with a specialized proteome and functions in many cellular roles. As such, LDs contribute to cellular signaling, protein and lipid homeostasis, metabolic diseases and inflammation. In line with the multitude of functions, LDs interact with many cellular organelles including mitochondria, peroxisomes, lysosomes, the endoplasmic retic...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.