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Current Opinion in Structural Biology Jun 2023Cells store lipids as a reservoir of metabolic energy and membrane component precursors in organelles called lipid droplets (LDs). LD formation occurs in the endoplasmic... (Review)
Review
Cells store lipids as a reservoir of metabolic energy and membrane component precursors in organelles called lipid droplets (LDs). LD formation occurs in the endoplasmic reticulum (ER) at LD assembly complexes (LDAC), consisting of an oligomeric core of seipin and accessory proteins. LDACs determine the sites of LD formation and are required for this process to occur normally. Seipin oligomers form a cage-like structure in the membrane that may serve to facilitate the phase transition of neutral lipids in the membrane to form an oil droplet within the LDAC. Modeling suggests that, as the LD grows, seipin anchors it to the ER bilayer and conformational shifts of seipin transmembrane segments open the LDAC dome toward the cytoplasm, enabling the emerging LD to egress from the ER.
Topics: Lipid Droplets; Proteins; Endoplasmic Reticulum; Lipids; Lipid Metabolism
PubMed: 37150040
DOI: 10.1016/j.sbi.2023.102606 -
Annual Review of Cell and Developmental... Oct 2020Lipid droplets (LDs) are endoplasmic reticulum-derived organelles that consist of a core of neutral lipids encircled by a phospholipid monolayer decorated with proteins.... (Review)
Review
Lipid droplets (LDs) are endoplasmic reticulum-derived organelles that consist of a core of neutral lipids encircled by a phospholipid monolayer decorated with proteins. As hubs of cellular lipid and energy metabolism, LDs are inherently involved in the etiology of prevalent metabolic diseases such as obesity and nonalcoholic fatty liver disease. The functions of LDs are regulated by a unique set of associated proteins, the LD proteome, which includes integral membrane and peripheral proteins. These proteins control key activities of LDs such as triacylglycerol synthesis and breakdown, nutrient sensing and signal integration, and interactions with other organelles. Here we review the mechanisms that regulate the composition of the LD proteome, such as pathways that mediate selective and bulk LD protein degradation and potential connections between LDs and cellular protein quality control.
Topics: Animals; Autophagy; Humans; Lipid Droplets; Proteins; Proteolysis; Proteome; Ubiquitin
PubMed: 33021827
DOI: 10.1146/annurev-cellbio-031320-101827 -
Trends in Cell Biology Nov 2021Seipin is a key protein in the assembly of cytoplasmic lipid droplets (cLDs) and their maintenance at endoplasmic reticulum (ER)-LD junctions; the absence of seipin... (Review)
Review
Seipin is a key protein in the assembly of cytoplasmic lipid droplets (cLDs) and their maintenance at endoplasmic reticulum (ER)-LD junctions; the absence of seipin results in generalized lipodystrophy. How seipin mediates LD dynamics and prevents lipodystrophy are not well understood. New evidence suggests that seipin attracts triglyceride monomers from the ER to sites of droplet formation. By contrast, seipin may not be directly involved in the assembly of nuclear LDs and may actually suppress their formation at a distance. Seipin promotes adipogenesis, but lipodystrophy may also involve postadipogenic effects. We hypothesize that among these are a cycle of runaway lipolysis and lipotoxicity caused by aberrant LDs, resulting in a depletion of fat stores and a failure of adipose and other cells to thrive.
Topics: Adipocytes; Adipose Tissue; Endoplasmic Reticulum; GTP-Binding Protein gamma Subunits; Humans; Lipid Droplets
PubMed: 34215489
DOI: 10.1016/j.tcb.2021.06.003 -
Oxidative Medicine and Cellular... 2022Abnormal lipid accumulation is commonly observed in diabetic cardiomyopathy (DC), which can create a lipotoxic microenvironment and damage cardiomyocytes. Lipid toxicity... (Review)
Review
Abnormal lipid accumulation is commonly observed in diabetic cardiomyopathy (DC), which can create a lipotoxic microenvironment and damage cardiomyocytes. Lipid toxicity is an important pathogenic factor due to abnormal lipid accumulation in DC. As a lipid droplet (LD) decomposition barrier, Plin5 can protect LDs from lipase decomposition and regulate lipid metabolism, which is involved in the occurrence and development of cardiovascular diseases. In recent years, studies have shown that Plin5 expression is involved in the pathogenesis of DC lipid toxicity, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and insulin resistance (IR) and has become a key target of DC research. Therefore, understanding the relationship between Plin5 and DC progression as well as the mechanism of this process is crucial for developing new therapeutic approaches and exploring new therapeutic targets. This review is aimed at exploring the latest findings and roles of Plin5 in lipid metabolism and DC-related pathogenesis, to explore possible clinical intervention approaches.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Humans; Lipid Droplets; Lipid Metabolism; Lipids; Perilipin-5
PubMed: 35509833
DOI: 10.1155/2022/2122856 -
Biochimica Et Biophysica Acta.... May 2018Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid... (Review)
Review
Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid monolayer. Although lipid storage is their most obvious function, LDs are far from inert as they participate in maintaining lipid homeostasis through lipid synthesis, metabolism, and transportation. Furthermore, they are involved in cell signaling and other molecular events closely associated with human disease such as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis, and others. The last decade has seen a great increase in the attention paid to LD biology. Regardless, many fundamental features of LD biology remain obscure. In this review, we will discuss key aspects of LD biology including their biogenesis, growth and regression. We will also summarize the current knowledge about the role LDs play in human disease, especially from the perspective of the dynamics of the associated proteins. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.
Topics: Animals; Energy Metabolism; Humans; Lipid Droplet Associated Proteins; Lipid Droplets; Lipid Metabolism; Metabolic Diseases; Signal Transduction
PubMed: 28739173
DOI: 10.1016/j.bbadis.2017.07.019 -
Cells Jul 2022Lipid droplets (LDs) are cellular organelles rich in neutral lipids such as triglycerides and cholesterol esters that are coated by a phospholipid monolayer and... (Review)
Review
Lipid droplets (LDs) are cellular organelles rich in neutral lipids such as triglycerides and cholesterol esters that are coated by a phospholipid monolayer and associated proteins. LDs are known to play important roles in the storage and availability of lipids in the cell and to serve as a source of energy reserve for the cell. However, these structures have also been related to oxidative stress, reticular stress responses, and reduced antigen presentation to T cells. Importantly, LDs are also known to modulate viral infection by participating in virus replication and assembly. Here, we review and discuss the interplay between neutral lipid metabolism and LDs in the replication cycle of different DNA viruses, identifying potentially new molecular targets for the treatment of viral infections.
Topics: Cholesterol Esters; DNA Virus Infections; Humans; Lipid Droplets; Lipid Metabolism; Triglycerides
PubMed: 35883666
DOI: 10.3390/cells11142224 -
Molecular and Cellular Endocrinology Feb 2017Steroidogenesis is a complex process through which cholesterol traffics to mitochondria and is converted via a series of enzymatic steps to steroid hormones. Although... (Review)
Review
Steroidogenesis is a complex process through which cholesterol traffics to mitochondria and is converted via a series of enzymatic steps to steroid hormones. Although the rate-limiting step in this process is the movement of cholesterol from the outer to the inner mitochondrial membrane via the actions of StAR, a continuous supply of cholesterol must be delivered to the outer mitochondrial membrane during active steroidogenesis and this is derived from multiple sources, including lipoprotein uptake, endogenous cholesterol synthesis and release from stores within cytoplasmic lipid droplets. A number of mechanisms have been suggested to contribute to cholesterol trafficking to mitochondria; however, there is no definitive consensus and this is particularly so in regards to trafficking from cytoplasmic lipid droplets. In this paper we review experiments in which we have surveyed the expression of SNARE proteins in steroidogenic tissue and cells and examined the role of SNAREs in mediating cholesterol movement from lipid droplets to the mitochondria based on multiple studies that identified SNAREs as components of cytoplasmic lipid droplets. We established and characterized an in vitro mitochondria reconstitution assay system that enabled us to examine the impact of adding recombinant SNARE proteins specifically on the movement of cholesterol from model lipid droplets to the outer mitochondrial membrane. Using this reconstitution assay system in combination with siRNA knockdown experiments in rat primary granulosa cells or in steroidogenic cell lines, we showed that several SNARE proteins are important components in the trafficking of cholesterol from lipid droplets to the mitochondria for steroidogenesis.
Topics: Animals; Biological Transport; Cholesterol; Humans; Lipid Droplets; Mitochondria; SNARE Proteins; Steroids
PubMed: 27477781
DOI: 10.1016/j.mce.2016.07.034 -
The Journal of Cell Biology Aug 2021In the ongoing conflict between eukaryotic cells and pathogens, lipid droplets (LDs) emerge as a choke point in the battle for nutrients. While many pathogens seek the... (Review)
Review
In the ongoing conflict between eukaryotic cells and pathogens, lipid droplets (LDs) emerge as a choke point in the battle for nutrients. While many pathogens seek the lipids stored in LDs to fuel an expensive lifestyle, innate immunity rewires lipid metabolism and weaponizes LDs to defend cells and animals. Viruses, bacteria, and parasites directly and remotely manipulate LDs to obtain substrates for metabolic energy, replication compartments, assembly platforms, membrane blocks, and tools for host colonization and/or evasion such as anti-inflammatory mediators, lipoviroparticles, and even exosomes. Host LDs counterattack such advances by synthesizing bioactive lipids and toxic nucleotides, organizing immune signaling platforms, and recruiting a plethora of antimicrobial proteins to provide a front-line defense against the invader. Here, we review the current state of this conflict. We will discuss why, when, and how LDs efficiently coordinate and precisely execute a plethora of immune defenses. In the age of antimicrobial resistance and viral pandemics, understanding innate immune strategies developed by eukaryotic cells to fight and defeat dangerous microorganisms may inform future anti-infective strategies.
Topics: Animals; Antimicrobial Cationic Peptides; Bacteria; Energy Metabolism; Evolution, Molecular; Host-Pathogen Interactions; Humans; Immunity, Innate; Lipid Droplets; Parasites; Signal Transduction; Viruses
PubMed: 34165498
DOI: 10.1083/jcb.202104005 -
Cellular Microbiology Jan 2017Lipid droplets were long considered to be simple storage structures, but they have recently been shown to be dynamic organelles involved in diverse biological processes,... (Review)
Review
Lipid droplets were long considered to be simple storage structures, but they have recently been shown to be dynamic organelles involved in diverse biological processes, including emerging roles in innate immunity. Various intracellular pathogens, including viruses, bacteria, and parasites, specifically target host lipid droplets during their life cycle. Viruses such as hepatitis C, dengue, and rotaviruses use lipid droplets as platforms for assembly. Bacteria, such as mycobacteria and Chlamydia, and parasites, such as trypanosomes, use host lipid droplets for nutritional purposes. The possible use of lipid droplets by intracellular pathogens, as part of an anti-immunity strategy, is an intriguing question meriting further investigation in the near future.
Topics: Animals; Bacteria; Humans; Lipid Droplets; Lipid Metabolism; Trypanosoma; Virus Assembly
PubMed: 27794207
DOI: 10.1111/cmi.12688 -
Biochemical and Biophysical Research... Sep 2023Lipid droplets are unique lipid storage organelles in hepatocytes. Lipophagy is a key mechanism of selective degradation of lipid droplets through lysosomes. It plays a... (Review)
Review
Lipid droplets are unique lipid storage organelles in hepatocytes. Lipophagy is a key mechanism of selective degradation of lipid droplets through lysosomes. It plays a crucial role in the prevention of metabolic liver disease, including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), and is a potential therapeutic target for treating these dysfunctions. In this review, we highlighted recent research and discussed advances in key proteins and molecular mechanisms related to lipophagy in liver disease. Reactive oxygen species (ROS) is an inevitable product of metabolism in alcohol-treated or high-fat-treated cells. Under this light, the potential role of ROS in autophagy in lipid droplet removal was initially explored to provide insights into the link between oxidative stress and metabolic liver disease. Subsequently, the current measures and drugs that treat NAFLD and AFLD through lipophagy regulation were summarized. The complexity of molecular mechanisms underlying lipophagy in hepatocytes and the need for further studies for their elucidation, as well as the status and limitations of current therapeutic measures and drugs, were also discussed.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Fatty Liver, Alcoholic; Reactive Oxygen Species; Lipid Metabolism; Liver; Autophagy; Metabolic Diseases; Lipid Droplets
PubMed: 37336123
DOI: 10.1016/j.bbrc.2023.06.030