Cell survival during complete nutrient deprivation depends on lipid droplet-fueled beta-oxidation of fatty acids
Autor: | Enrique Claro, Eleni Nintou, Fernando Picatoste, Ainara G. Cabodevilla, Laura Sánchez-Caballero, Violeta G. Boiadjieva, Albert Gubern |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
endocrine system
Programmed cell death Cell Survival Lipolysis education Àcids grassos CHO Cells Biology Stress Biochemistry Cricetulus Cell Line Tumor Ceramide kinase Lipid droplet Autophagy Animals Humans Viability assay Molecular Biology Beta oxidation Lipid Droplet L-Lactate Dehydrogenase Cell Death Lipogenesis Fatty Acids technology industry and agriculture Lipid metabolism Cell Biology Lipid Metabolism Lipids eye diseases Culture Media Rats Cell biology Oxygen Glucose Gene Expression Regulation Microscopy Fluorescence Starvation Astrocytes Lípids lipids (amino acids peptides and proteins) Nutrició -- Necessitats Fatty Acid Oxidation Oxidation-Reduction Biogenesis HeLa Cells |
Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Recercat. Dipósit de la Recerca de Catalunya instname |
Popis: | Cells exposed to stress of different origins synthesize triacylglycerols and generate lipid droplets (LD), but the physiological relevance of this response is uncertain. Using complete nutrient deprivation of cells in culture as a simple model of stress, we have addressed whether LD biogenesis has a protective role in cells committed to die. Complete nutrient deprivation induced the biogenesis of LD in human LN18 glioblastoma and HeLa cells and also in CHO and rat primary astrocytes. In all cell types, death was associated with LD depletion and was accelerated by blocking LD biogenesis after pharmacological inhibition of Group IVA phospholipase A2 (cPLA2α) or down-regulation of ceramide kinase. Nutrient deprivation also induced β-oxidation of fatty acids that was sensitive to cPLA2α inhibition, and cell survival in these conditions became strictly dependent on fatty acid catabolism. These results show that, during nutrient deprivation, cell viability is sustained by β-oxidation of fatty acids that requires biogenesis and mobilization of LD. Cellular stress leading to cell death induces the formation of lipid droplets. Nutrient deprivation induces LD biogenesis and mobilization, fueling fatty acid oxidation to sustain cell viability. β-Oxidation requires biogenesis and mobilization of LD. The role of LD in cell survival and β-oxidation might provide new potential targets for antitumor therapy. This work was supported in part by Spanish Ministry of Economy Grants BFU2009-07823 and BFU2012-34987). |
Databáze: | OpenAIRE |
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