Lipid Droplets in Cancer
Lipid droplets have a unique structure among organelles consisting of a dense hydrophobic core of neutral lipids surrounded by a single layer of phospholipids decorated with various proteins. Often labeled merely as passive fat storage repositories, they
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Lipid Droplets in Cancer Toni Petan
Contents 1 Introduction 2 Lipid Droplets Are Dynamic Organelles 2.1 Lipid Droplets Are Versatile Ensembles of Lipids and Proteins 2.2 Lipid Droplet Biogenesis Occurs at the Crossroads of Membrane and Neutral Lipid Metabolism 2.3 Lipid Droplet Breakdown Occurs via Lipolysis or Lipophagy 3 Lipid Droplets Are at the Core of Cancer Metabolic Reprogramming 3.1 Cancer Cells Use Ingenious Ways of Lipid Acquisition That Converge at the Lipid Droplet 3.2 Lipid Droplets and Nutrient Scavenging 3.3 Lipid Droplets Maintain Membrane Unsaturation During Stress 3.4 Lipid Droplets Match Nutrient Fluctuations with Cell Growth and Survival 3.5 When the Going Gets Tough, Lipid Droplets Team Up with Autophagy 3.6 Lipid Droplets, Lipid Peroxidation, and Ferroptosis in Cancer 4 Conclusions and Perspectives References
Abstract Lipid droplets have a unique structure among organelles consisting of a dense hydrophobic core of neutral lipids surrounded by a single layer of phospholipids decorated with various proteins. Often labeled merely as passive fat storage repositories, they in fact have a remarkably dynamic life cycle. Being formed within the endoplasmic reticulum membrane, lipid droplets rapidly grow, shrink, traverse the cytosol, and engage in contacts with other organelles to exchange proteins and lipids. Their lipid and protein composition changes dynamically in response to cellular states and nutrient availability. Remarkably, their biogenesis is induced when cells experience various forms of nutrient, energy, and redox imbalances, including lipid excess and complete nutrient deprivation. Cancer cells are continuously exposed to nutrient and oxygen fluctuations and have the capacity to switch between alternative nutrient acquisition and metabolic pathways in order to strive T. Petan (*) Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia e-mail: [email protected]
T. Petan
even during severe stress. Their supply of lipids is ensured by a series of nutrient uptake and scavenging mechanisms, upregulation of de novo lipid synthesis, repurposing of their structural lipids via enzymatic remodeling, or lipid recycling through autophagy. Importantly, most of these pathways of lipid acquisition converge at lipid droplets, which combine different lipid fluxes and control their usage based on specific cellular needs. It is thus not surprising that lipid droplet breakdown is an elaborately regulated process that occurs via a complex interplay of neutral lipases and autophagic degradation. Cancer cells employ lipid droplets to ensure energy production and redox balance, modulate autophagy, drive membrane synthesis, and control its composition, thereby minimizing stress and fostering tumor progression. As regulators of (poly)unsaturated fatty acid trafficking, lipid droplets are also emerging as modulators of lipid peroxidation and sensitivity to ferroptosis. Clearly, dysregulated lipid droplet turnover may also be detrimental to cancer cells, which should provide pot
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