Lipid Droplets in Cancer.
Autophagy
Cancer
Fatty acid
Ferroptosis
Lipid droplets
Metabolism
Stress
Journal
Reviews of physiology, biochemistry and pharmacology
ISSN: 0303-4240
Titre abrégé: Rev Physiol Biochem Pharmacol
Pays: Germany
ID NLM: 0434624
Informations de publication
Date de publication:
2023
2023
Historique:
pubmed:
20
10
2020
medline:
1
2
2023
entrez:
19
10
2020
Statut:
ppublish
Résumé
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 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 potential therapeutic opportunities in the future. In this review, we explore how lipid droplets consolidate lipid acquisition and trafficking pathways in order to match lipid supply with the requirements for cancer cell survival, growth, and metastasis.
Substances chimiques
Phospholipids
0
Proteins
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
53-86Informations de copyright
© 2020. The Author(s).
Références
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