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Nature Reviews. Molecular Cell Biology Mar 2019Lipid droplets are storage organelles at the centre of lipid and energy homeostasis. They have a unique architecture consisting of a hydrophobic core of neutral lipids,... (Review)
Review
Lipid droplets are storage organelles at the centre of lipid and energy homeostasis. They have a unique architecture consisting of a hydrophobic core of neutral lipids, which is enclosed by a phospholipid monolayer that is decorated by a specific set of proteins. Originating from the endoplasmic reticulum, lipid droplets can associate with most other cellular organelles through membrane contact sites. It is becoming apparent that these contacts between lipid droplets and other organelles are highly dynamic and coupled to the cycles of lipid droplet expansion and shrinkage. Importantly, lipid droplet biogenesis and degradation, as well as their interactions with other organelles, are tightly coupled to cellular metabolism and are critical to buffer the levels of toxic lipid species. Thus, lipid droplets facilitate the coordination and communication between different organelles and act as vital hubs of cellular metabolism.
Topics: Animals; Endoplasmic Reticulum; Homeostasis; Humans; Lipid Droplets; Lipid Metabolism; Phospholipids
PubMed: 30523332
DOI: 10.1038/s41580-018-0085-z -
Annual Review of Cell and Developmental... Oct 2017Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids for energy or membrane synthesis and act as hubs for metabolic processes. Cells generate LDs de... (Review)
Review
Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids for energy or membrane synthesis and act as hubs for metabolic processes. Cells generate LDs de novo, converting cells to emulsions with LDs constituting the dispersed oil phase in the aqueous cytoplasm. Here we review our current view of LD biogenesis. We present a model of LD formation from the ER in distinct steps and highlight the biology of proteins that govern this biophysical process. Areas of incomplete knowledge are identified, as are connections with physiology and diseases linked to alterations in LD biology.
Topics: Animals; Biophysical Phenomena; Humans; Lipid Droplets; Models, Biological; Proteins; Triglycerides
PubMed: 28793795
DOI: 10.1146/annurev-cellbio-100616-060608 -
Nature Reviews. Endocrinology Aug 2023Ubiquitous yet unique, lipid droplets are intracellular organelles that are increasingly being recognized for their versatility beyond energy storage. Advances... (Review)
Review
Ubiquitous yet unique, lipid droplets are intracellular organelles that are increasingly being recognized for their versatility beyond energy storage. Advances uncovering the intricacies of their biogenesis and the diversity of their physiological and pathological roles have yielded new insights into lipid droplet biology. Despite these insights, the mechanisms governing the biogenesis and functions of lipid droplets remain incompletely understood. Moreover, the causal relationship between the biogenesis and function of lipid droplets and human diseases is poorly resolved. Here, we provide an update on the current understanding of the biogenesis and functions of lipid droplets in health and disease, highlighting a key role for lipid droplet biogenesis in alleviating cellular stresses. We also discuss therapeutic strategies of targeting lipid droplet biogenesis, growth or degradation that could be applied in the future to common diseases, such as cancer, hepatic steatosis and viral infection.
Topics: Humans; Lipid Droplets; Lipid Metabolism; Lipogenesis
PubMed: 37221402
DOI: 10.1038/s41574-023-00845-0 -
Nature Reviews. Nephrology Oct 2023Chronic kidney disease (CKD) is a global health problem with rising incidence and prevalence. Among several pathogenetic mechanisms responsible for disease progression,... (Review)
Review
Chronic kidney disease (CKD) is a global health problem with rising incidence and prevalence. Among several pathogenetic mechanisms responsible for disease progression, lipid accumulation in the kidney parenchyma might drive inflammation and fibrosis, as has been described in fatty liver diseases. Lipids and their metabolites have several important structural and functional roles, as they are constituents of cell and organelle membranes, serve as signalling molecules and are used for energy production. However, although lipids can be stored in lipid droplets to maintain lipid homeostasis, lipid accumulation can become pathogenic. Understanding the mechanisms linking kidney parenchymal lipid accumulation to CKD of metabolic or non-metabolic origin is challenging, owing to the tremendous variety of lipid species and their functional diversity across different parenchymal cells. Nonetheless, multiple research reports have begun to emphasize the effect of dysregulated kidney lipid metabolism in CKD progression. For example, altered cholesterol and fatty acid metabolism contribute to glomerular and tubular cell injury. Newly developed lipid-targeting agents are being tested in clinical trials in CKD, raising expectations for further therapeutic development in this field.
Topics: Humans; Lipid Droplets; Kidney; Renal Insufficiency, Chronic; Inflammation; Lipids; Lipid Metabolism
PubMed: 37500941
DOI: 10.1038/s41581-023-00741-w -
The Journal of Cell Biology Jul 2021Lipid droplets are dynamic intracellular lipid storage organelles that respond to the physiological state of cells. In addition to controlling cell metabolism, they play... (Review)
Review
Lipid droplets are dynamic intracellular lipid storage organelles that respond to the physiological state of cells. In addition to controlling cell metabolism, they play a protective role for many cellular stressors, including oxidative stress. Despite prior descriptions of lipid droplets appearing in the brain as early as a century ago, only recently has the role of lipid droplets in cells found in the brain begun to be understood. Lipid droplet functions have now been described for cells of the nervous system in the context of development, aging, and an increasing number of neuropathologies. Here, we review the basic mechanisms of lipid droplet formation, turnover, and function and discuss how these mechanisms enable lipid droplets to function in different cell types of the nervous system under healthy and pathological conditions.
Topics: Aging; Animals; Humans; Lipid Droplets; Lipid Metabolism; Nervous System; Oxidative Stress
PubMed: 34152362
DOI: 10.1083/jcb.202102136 -
Cell Metabolism Apr 2019The isolation and biochemical characterization of lipid droplet (LD)-associated mitochondria revealed the capacity of the cell to produce and maintain distinct... (Review)
Review
The isolation and biochemical characterization of lipid droplet (LD)-associated mitochondria revealed the capacity of the cell to produce and maintain distinct mitochondrial populations carrying disparate proteome and dissimilar capacities to oxidize fatty acids and pyruvate. With mitochondrial motility being a central parameter determining mitochondrial fusion, adherence to LDs provides a mechanism by which peridroplet mitochondria (PDM) remain segregated from cytoplasmic mitochondria (CM). The existence of metabolically distinct subpopulations provides an explanation for the capacity of mitochondria within the individual cell to be involved simultaneously in fatty acid oxidation and LD formation. The mechanisms that deploy mitochondria to the LD and the dysfunctions that result from unbalanced proportions of PDM and CM remain to be explored. Understanding the roles and regulation of mitochondrial tethering to LDs offers new points of intervention in metabolic diseases.
Topics: Animals; Humans; Lipid Droplets; Lipid Metabolism; Mitochondria; Mitochondrial Dynamics
PubMed: 30905670
DOI: 10.1016/j.cmet.2019.02.011 -
Journal of Hepatology Apr 2022Lipid droplets (LDs) are complex and metabolically active organelles. They are composed of a neutral lipid core surrounded by a monolayer of phospholipids and proteins.... (Review)
Review
Lipid droplets (LDs) are complex and metabolically active organelles. They are composed of a neutral lipid core surrounded by a monolayer of phospholipids and proteins. LD accumulation in hepatocytes is the distinctive characteristic of non-alcoholic fatty liver disease (NAFLD), which is a chronic, heterogeneous liver condition that can progress to liver fibrosis and hepatocellular carcinoma. Though recent research has improved our understanding of the mechanisms linking LD accumulation to NAFLD progression, numerous aspects of LD biology are either poorly understood or unknown. In this review, we provide a description of several key mechanisms that contribute to LD accumulation in hepatocytes, favouring NAFLD progression. First, we highlight the importance of LD architecture and describe how the dysregulation of LD biogenesis leads to endoplasmic reticulum stress and inflammation. This is followed by an analysis of the causal nexus that exists between LD proteome composition and LD degradation. Finally, we describe how the increase in size of LDs causes activation of hepatic stellate cells, leading to liver fibrosis and hepatocellular carcinoma. We conclude that acquiring a more sophisticated understanding of LD biology will provide crucial insights into the heterogeneity of NAFLD and assist in the development of therapeutic approaches for this liver disease.
Topics: Carcinoma, Hepatocellular; Humans; Lipid Droplets; Lipid Metabolism; Liver; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease
PubMed: 34793866
DOI: 10.1016/j.jhep.2021.11.009 -
Nature Cell Biology Mar 2024Lipid droplets are dynamic organelles that store neutral lipids, serve the metabolic needs of cells, and sequester lipids to prevent lipotoxicity and membrane damage.... (Review)
Review
Lipid droplets are dynamic organelles that store neutral lipids, serve the metabolic needs of cells, and sequester lipids to prevent lipotoxicity and membrane damage. Here we review the current understanding of the mechanisms of lipid droplet biogenesis and turnover, the transfer of lipids and metabolites at membrane contact sites, and the role of lipid droplets in regulating fatty acid flux in lipotoxicity and cell death.
Topics: Lipid Droplets; Lipid Metabolism; Homeostasis; Fatty Acids
PubMed: 38454048
DOI: 10.1038/s41556-024-01364-4 -
Seminars in Cell & Developmental Biology Dec 2020In cells, lipids are stored in lipid droplets, dynamic organelles that adapt their size, abundance, lipid and protein composition and organelle interactions to metabolic... (Review)
Review
In cells, lipids are stored in lipid droplets, dynamic organelles that adapt their size, abundance, lipid and protein composition and organelle interactions to metabolic changes. Lipid droplet accumulation in the liver is the hallmark of non-alcoholic fatty liver disease (NAFLD). Due to the prevalence of obesity, the strongest risk factor for steatosis, NAFLD and its associated complications are currently affecting more than 1 billion people worldwide. Here, we review how triglyceride and phospholipid homeostasis are regulated in hepatocytes and how imbalances between lipid storage, degradation and lipoprotein secretion lead to NAFLD. We discuss how organelle interactions are altered in NAFLD and provide insights how NAFLD progression is associated with changes in hepatocellular signaling and organ-crosstalk. Finally, we highlight unsolved questions in hepatic LD and lipoprotein biology and give an outlook on therapeutic options counteracting hepatic lipid accumulation.
Topics: Animals; Fatty Liver; Homeostasis; Humans; Lipid Droplets; Lipid Metabolism; Liver
PubMed: 32444289
DOI: 10.1016/j.semcdb.2020.04.011 -
Biochemical and Biophysical Research... Jan 2019The synthesis, storage, and degradation of lipids are highly regulated processes. Impaired lipid metabolism is implicated in inflammation and cell death. Although...
The synthesis, storage, and degradation of lipids are highly regulated processes. Impaired lipid metabolism is implicated in inflammation and cell death. Although ferroptosis is a recently described form of regulated cell death driven by lipid peroxidation, the impact of lipid droplets on ferroptosis remains unidentified. Here, we demonstrate that lipophagy, the autophagic degradation of intracellular lipid droplets, promotes RSL3-induced ferroptotic cell death in hepatocytes. Lipid droplet accumulation is increased at the early stage but decreased at the late stage of ferroptosis in mouse or human hepatocytes. Importantly, either genetically enhancing TPD52-dependent lipid storage or blocking ATG5-and RAB7A-dependent lipid degradation prevents RSL3-induced lipid peroxidation and subsequent ferroptosis in vitro and in vivo. These studies support an antioxidant role for lipid droplets in cell death and suggest novel strategies for the inhibition of ferroptosis by targeting the lipophagy pathway.
Topics: Animals; Apoptosis; Autophagy; Autophagy-Related Protein 5; Carbolines; Hep G2 Cells; Humans; Iron; Lipid Droplets; Lipid Metabolism; Mice; Neoplasm Proteins; rab GTP-Binding Proteins; rab7 GTP-Binding Proteins
PubMed: 30545638
DOI: 10.1016/j.bbrc.2018.12.039