Cell survival during complete nutrient deprivation depends on lipid droplet-fueled β-oxidation of fatty acids.
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.
From the Institut de Neurociències and Departament de Bioquímica i Biologia Molecular, Edifici M2, Campus de la UAB, Universitat Autònoma de Barcelona, E-08193 Cerdanyola del Vallès and.
Ainara G
AG
Cabodevilla
Laura
L
Sánchez-Caballero
Eleni
E
Nintou
Violeta G
VG
Boiadjieva
Fernando
F
Picatoste
Albert
A
Gubern
Enrique
E
Claro
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001343:Autophagy; D016466:CHO Cells; D045744:Cell Line, Tumor; D002470:Cell Survival; D003412:Cricetulus; D003470:Culture Media / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008066:Lipolysis; D008856:Microscopy, Fluorescence; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D051381:Rats
D003470:Culture Media; D005227:Fatty Acids; D008055:Lipids; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D010100:Oxygen
Cell Death; Fatty Acid Oxidation; Lipid Droplet; Lipogenesis; Lipolysis; Starvation; Stress