scholarly journals A Novel Photosensitizer for Lipid Droplet–Location Photodynamic Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiang Xia ◽  
Ran Wang ◽  
Yingqi Hu ◽  
WeiJian Liu ◽  
Ting Liu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Fluorescence Imaging ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Biological Processes ◽  
Cellular Organelle ◽  
Potential Target ◽  
Ic50 Value ◽  
Good Biocompatibility

Lipid droplets (LDs), an extremely important cellular organelle, are responsible for the storage of neutral lipids in multiple biological processes, which could be a potential target site for photodynamic therapy (PDT) of cancer. Herein, a lipid droplet–targeted photosensitizer (BODSeI) is developed, allowing for fluorescence imaging–guided PDT. Owing to the location of lipid droplets, BODSeI demonstrates enhanced PDT efficiency with an extremely low IC50 value (around 125 nM). Besides, BODSeI shows good biocompatibility and high photostability. Therefore, BODSeI is promising for droplet-location PDT, which may trigger wide interest for exploring the pathway of lipid droplet–location PDT.

scholarly journals Motility Plays an Important Role in the Lifetime of Mammalian Lipid Droplets

2021 ◽  
Vol 22 (8) ◽  
pp. 3802
Author(s):  
Yi Jin ◽  
Zhuqing Ren ◽  
Yanjie Tan ◽  
Pengxiang Zhao ◽  
Jian Wu
Keyword(s):  
Signal Transduction ◽  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Molecular Basis ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Future Research ◽  
Biological Processes ◽  
Cellular Processes ◽  
Resistance To Stress

The lipid droplet is a kind of organelle that stores neutral lipids in cells. Recent studies have found that in addition to energy storage, lipid droplets also play an important role in biological processes such as resistance to stress, immunity, cell proliferation, apoptosis, and signal transduction. Lipid droplets are formed at the endoplasmic reticulum, and mature lipid droplets participate in various cellular processes. Lipid droplets are decomposed by lipase and lysosomes. In the life of a lipid droplet, the most important thing is to interact with other organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and autophagic lysosomes. The interaction between lipid droplets and other organelles requires them to be close to each other, which inevitably involves the motility of lipid droplets. In fact, through many microscopic observation techniques, researchers have discovered that lipid droplets are highly dynamic organelles that move quickly. This paper reviews the process of lipid droplet motility, focusing on explaining the molecular basis of lipid droplet motility, the factors that regulate lipid droplet motility, and the influence of motility on the formation and decomposition of lipid droplets. In addition, this paper also proposes several unresolved problems for lipid droplet motility. Finally, this paper makes predictions about the future research of lipid droplet motility.

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

2011 ◽  
Vol 195 (6) ◽  
pp. 953-963 ◽  
Author(s):  
Jingyi Gong ◽  
Zhiqi Sun ◽  
Lizhen Wu ◽  
Wenyi Xu ◽  
Nicole Schieber ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Lipid Droplets ◽  
Droplet Growth ◽  
Biological Processes ◽  
Lipid Transfer ◽  
Wild Type ◽  
Lipid Exchange ◽  
Biophysical Analysis ◽  
Molecular Components ◽  
Cellular Organelles

Lipid droplets (LDs) are dynamic cellular organelles that control many biological processes. However, molecular components determining LD growth are poorly understood. Genetic analysis has indicated that Fsp27, an LD-associated protein, is important in controlling LD size and lipid storage in adipocytes. In this paper, we demonstrate that Fsp27 is focally enriched at the LD–LD contacting site (LDCS). Photobleaching revealed the occurrence of lipid exchange between contacted LDs in wild-type adipocytes and Fsp27-overexpressing cells but not Fsp27-deficient adipocytes. Furthermore, live-cell imaging revealed a unique Fsp27-mediated LD growth process involving a directional net lipid transfer from the smaller to larger LDs at LDCSs, which is in accordance with the biophysical analysis of the internal pressure difference between the contacting LD pair. Thus, we have uncovered a novel molecular mechanism of LD growth mediated by Fsp27.

scholarly journals Dictyostelium Lipid Droplets Host Novel Proteins

2013 ◽  
Vol 12 (11) ◽  
pp. 1517-1529 ◽  
Author(s):  
Xiaoli Du ◽  
Caroline Barisch ◽  
Peggy Paschke ◽  
Cornelia Herrfurth ◽  
Oliver Bertinetti ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Unsaturated Fatty Acids ◽  
Neutral Lipids ◽  
Saturated Fatty Acids ◽  
Endoplasmic Reticulum Membrane ◽  
Hydrophobic Core ◽  
Content Type

ABSTRACT Across all kingdoms of life, cells store energy in a specialized organelle, the lipid droplet. In general, it consists of a hydrophobic core of triglycerides and steryl esters surrounded by only one leaflet derived from the endoplasmic reticulum membrane to which a specific set of proteins is bound. We have chosen the unicellular organism Dictyostelium discoideum to establish kinetics of lipid droplet formation and degradation and to further identify the lipid constituents and proteins of lipid droplets. Here, we show that the lipid composition is similar to what is found in mammalian lipid droplets. In addition, phospholipids preferentially consist of mainly saturated fatty acids, whereas neutral lipids are enriched in unsaturated fatty acids. Among the novel protein components are LdpA, a protein specific to Dictyostelium , and Net4, which has strong homologies to mammalian DUF829/Tmem53/NET4 that was previously only known as a constituent of the mammalian nuclear envelope. The proteins analyzed so far appear to move from the endoplasmic reticulum to the lipid droplets, supporting the concept that lipid droplets are formed on this membrane.

scholarly journals Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yoel A. Klug ◽  
Justin C. Deme ◽  
Robin A. Corey ◽  
Mike F. Renne ◽  
Phillip J. Stansfeld ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Endoplasmic Reticulum ◽  
Molecular Dynamics Simulation ◽  
Membrane Protein ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Dynamics Simulation ◽  
Transmembrane Segments ◽  
Lipid Droplet Formation

AbstractLipid droplets (LDs) are universal lipid storage organelles with a core of neutral lipids, such as triacylglycerols, surrounded by a phospholipid monolayer. This unique architecture is generated during LD biogenesis at endoplasmic reticulum (ER) sites marked by Seipin, a conserved membrane protein mutated in lipodystrophy. Here structural, biochemical and molecular dynamics simulation approaches reveal the mechanism of LD formation by the yeast Seipin Sei1 and its membrane partner Ldb16. We show that Sei1 luminal domain assembles a homooligomeric ring, which, in contrast to other Seipins, is unable to concentrate triacylglycerol. Instead, Sei1 positions Ldb16, which concentrates triacylglycerol within the Sei1 ring through critical hydroxyl residues. Triacylglycerol recruitment to the complex is further promoted by Sei1 transmembrane segments, which also control Ldb16 stability. Thus, we propose that LD assembly by the Sei1/Ldb16 complex, and likely other Seipins, requires sequential triacylglycerol-concentrating steps via distinct elements in the ER membrane and lumen.

scholarly journals Lipid Droplet-Associated Factors, PNPLA3, TM6SF2, and HSD17B Proteins in Hepatopancreatobiliary Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4391
Author(s):  
Yoshiaki Sunami ◽  
Artur Rebelo ◽  
Jörg Kleeff
Keyword(s):  
Liver Cancer ◽  
Lipid Droplet ◽  
Associated Factors ◽  
Lipid Droplets ◽  
Cancer Metabolism ◽  
Neutral Lipids ◽  
Cancer Type ◽  
Hepatic Diseases ◽  
Cell Type Specific ◽  
Intracellular Organelles

Pancreatic and liver cancer are leading causes of cancer deaths, and by 2030, they are projected to become the second and the third deadliest cancer respectively. Cancer metabolism, especially lipid metabolism, plays an important role in progression and metastasis of many types of cancer, including pancreatic and liver cancer. Lipid droplets are intracellular organelles that store neutral lipids, but also act as molecular messengers, and signaling factors. It is becoming increasingly evident that alterations in the regulation of lipid droplets and their associated factors influence the risk of developing not only metabolic disease but also fibrosis and cancer. In the current review article, we summarized recent findings concerning the roles of lipid droplet-associated factors, patatin-like phospholipase domain-containing 3, Transmembrane 6 superfamily member 2, and 17β-hydroxysteroid dehydrogenase 11 and 13 as well as genetic variants in pancreatic and hepatic diseases. A better understanding of cancer type- and cell type-specific roles of lipid droplet-associated factors is important for establishing new therapeutic options in the future.

scholarly journals Chitosan oligosaccharide decorated liposomes combined with TH302 for photodynamic therapy in triple negative breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yinan Ding ◽  
Rui Yang ◽  
Weiping Yu ◽  
Chunmei Hu ◽  
Zhiyuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Fluorescence Imaging ◽  
Triple Negative ◽  
Chitosan Oligosaccharide ◽  
Antitumor Effects ◽  
Imaging Capability ◽  
Good Biocompatibility

Abstract Background Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy. Results Compared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo. Conclusion The impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC. Graphic abstract

Halogen-Modified Carbazole Derivatives for Lipid Droplet-Specific Bioimaging and Two-Photon Photodynamic Therapy

The Analyst ◽  
2021 ◽  
Author(s):  
Yupeng Tian ◽  
Wen Li Du ◽  
Xin Lu ◽  
Tong Yuan ◽  
Zhimin Sun ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Biological Research ◽  
Metabolic Processes ◽  
Carbazole Derivatives ◽  
Two Photon

Lipid droplets (LDs) are dynamic multifunctional organelles that participate in the regulation of many metabolic processes, visualization of which is necessary for biological research. In this work, series of two-photon...

scholarly journals Amino acid starvation inhibits autophagy in lipid droplet-deficient cells through mitochondrial dysfunction

2020 ◽  
Vol 477 (18) ◽  
pp. 3613-3623
Author(s):  
Pierre Voisin ◽  
Marianne Bernard ◽  
Thierry Bergès ◽  
Matthieu Régnacq
Keyword(s):  
Amino Acid ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Nitrogen Starvation ◽  
Neutral Lipids ◽  
Normal Growth ◽  
Growth Conditions ◽  
Amino Acid Starvation ◽  
Yeast Saccharomyces Cerevisiae ◽  
Functional Link

Lipid droplets are ubiquitous organelles in eukaryotes that act as storage sites for neutral lipids. Under normal growth conditions, they are not required in the yeast Saccharomyces cerevisiae. However, recent works have shown that lipid droplets are required for autophagy to proceed in response to nitrogen starvation and that they play an essential role in maintaining ER homeostasis. Autophagy is a major catabolic pathway that helps degradation and recycling of potentially harmful proteins and organelles. It can be pharmacologically induced by rapamycin even in the absence of lipid droplets. Here, we show that amino acid starvation is responsible for autophagy failure in lipid droplet-deficient yeast. It not only fails to induce autophagy but also inhibits rapamycin-induced autophagy. The general amino acid control pathway is not involved in this paradoxical effect of amino acid shortage. We correlate the autophagy failure with mitochondria aggregation and we show that amino acid starvation-induced autophagy is restored in lipid droplet-deficient yeast by increasing mitochondrial biomass physiologically (respiration) or genetically (REG1 deletion). Our results establish a new functional link between lipid droplets, ER and mitochondria during nitrogen starvation-induced autophagy.

scholarly journals A near-infrared AIEgen for specific imaging of lipid droplets

2016 ◽  
Vol 52 (35) ◽  
pp. 5957-5960 ◽  
Author(s):  
Miaomiao Kang ◽  
Xinggui Gu ◽  
Ryan T. K. Kwok ◽  
Chris W. T. Leung ◽  
Jacky W. Y. Lam ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Lipid Droplets ◽  
Near Infrared ◽  
High Brightness ◽  
Good Biocompatibility ◽  
Specific Lipid

A new near-infrared AIE luminogen is developed for specific lipid droplet imaging with high brightness, good biocompatibility and superior photostability.

Mechanisms of lipid droplet biogenesis

2019 ◽  
Vol 476 (13) ◽  
pp. 1929-1942 ◽  
Author(s):  
Kent D. Chapman ◽  
Mina Aziz ◽  
John M. Dyer ◽  
Robert T. Mullen
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Steryl Esters ◽  
Evolutionarily Conserved ◽  
Compare And Contrast ◽  
In Cells

Abstract Lipid droplets (LDs) are organelles that compartmentalize nonbilayer-forming lipids in the aqueous cytoplasm of cells. They are ubiquitous in most organisms, including in animals, protists, plants and microorganisms. In eukaryotes, LDs are believed to be derived by a budding and scission process from the surface of the endoplasmic reticulum, and this occurs concomitantly with the accumulation of neutral lipids, most often triacylglycerols and steryl esters. Overall, the mechanisms underlying LD biogenesis are difficult to generalize, in part because of the involvement of different sets of both evolutionarily conserved and organism-specific LD-packaging proteins. Here, we briefly compare and contrast these proteins and the allied processes responsible for LD biogenesis in cells of animals, yeasts and plants.

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