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
Jazyk: angličtina
Rok vydání: 2013
Předmět:
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