Lipid droplet biogenesis induced by stress involves triacylglycerol synthesis that depends on group VIA phospholipase A2.
This work investigates the metabolic origin of triacylglycerol (TAG) formed during lipid droplet (LD) biogenesis induced by stress. Cytotoxic inhibitors of fatty acid synthase induced TAG synthesis and LD biogenesis in CHO-K1 cells, in the absence of external sources of fatty acids. TAG synthesis was required for LD biogenesis and was sensitive to inhibition and down-regulation of the expression of group VIA phospholipase A(2) (iPLA(2)-VIA). Induction of stress with acidic pH, C(2)-ceramide, tunicamycin, or deprivation of glucose also stimulated TAG synthesis and LD formation in a manner dependent on iPLA(2)-VIA. Overexpression of the enzyme enhanced TAG synthesis from endogenous fatty acids and LD occurrence. During stress, LD biogenesis but not TAG synthesis required phosphorylation and activation of group IVA PLA(2) (cPLA(2)alpha). The results demonstrate that iPLA(2)-VIA provides fatty acids for TAG synthesis while cPLA(2)alpha allows LD biogenesis. LD biogenesis during stress may be a survival strategy, recycling structural phospholipids into energy-generating substrates.
Gubern
Albert
A
Institut de Neurociències and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona (UAB), Edifici M2, Campus de la UAB, Barcelona E-08193, Spain.
Barceló-Torns
Miquel
M
Casas
Javier
J
Barneda
David
D
Masgrau
Roser
R
Picatoste
Fernando
F
Balsinde
Jesús
J
Balboa
María A
MA
Claro
Enrique
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005227:Fatty Acids; D005434:Flow Cytometry; D005453:Fluorescence; D005947:Glucose / Q000172:deficiency; D054522:Group VI Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D018384:Oxidative Stress; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014280:Triglycerides / Q000096:biosynthesis*; D014415:Tunicamycin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D005227:Fatty Acids; C064769:N-acetylsphingosine; D034741:RNA, Small Interfering; D014280:Triglycerides; D014415:Tunicamycin; D064429:Fatty Acid Synthases; D054522:Group VI Phospholipases A2; D010738:Type C Phospholipases; D005947:Glucose; D013110:Sphingosine; D002118:Calcium