RT info:eu-repo/semantics/article
T1 Group IVA Phospholipase A2 Is Necessary for the Biogenesis of Lipid Droplets
A1 Gubern, Albert
A1 Casas, Javier
A1 Barceló-Torns, Miquel
A1 Barneda, David
A1 de la Rosa, Xavier
A1 Masgrau, Roser
A1 Picatoste, Fernando
A1 Balsinde, Jesús
A1 Balboa, María A.
A1 Claro, Enrique
AB Lipid droplets (LD) are organelles present in all cell types, consisting of a hydrophobic core of triacylglycerols and cholesteryl esters, surrounded by a monolayer of phospholipids and cholesterol. This work shows that LD biogenesis induced by serum, by long-chain fatty acids, or the combination of both in CHO-K1 cells was prevented by phospholipase A(2) inhibitors with a pharmacological profile consistent with the implication of group IVA cytosolic phospholipase A(2) (cPLA(2)alpha). Knocking down cPLA(2)alpha expression with short interfering RNA was similar to pharmacological inhibition in terms of enzyme activity and LD biogenesis. A Chinese hamster ovary cell clone stably expressing an enhanced green fluorescent protein-cPLA(2)alpha fusion protein (EGFP-cPLA(2)) displayed higher LD occurrence under basal conditions and upon LD induction. Induction of LD took place with concurrent phosphorylation of cPLA(2)alpha at Ser(505). Transfection of a S505A mutant cPLA(2)alpha showed that phosphorylation at Ser(505) is key for enzyme activity and LD formation. cPLA(2)alpha contribution to LD biogenesis was not because of the generation of arachidonic acid, nor was it related to neutral lipid synthesis. cPLA(2)alpha inhibition in cells induced to form LD resulted in the appearance of tubulo-vesicular profiles of the smooth endoplasmic reticulum, compatible with a role of cPLA(2)alpha in the formation of nascent LD from the endoplasmic reticulum.
SN 0021-9258
YR 2008
FD 2008
LK https://uvadoc.uva.es/handle/10324/64293
UL https://uvadoc.uva.es/handle/10324/64293
LA eng
NO The Journal of biological chemistry 283, 27369–27382 (2008).
NO Producción Científica
DS UVaDOC
RD 01-jun-2024