Lipid Droplet Biogenesis Induced by Stress Involves Triacylglycerol Synthesis That Depends on Group VIA Phospholipase A2
Lipid Droplet Biogenesis Induced by Stress Involves Triacylglycerol Synthesis That Depends on Group VIA Phospholipase A2
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DOI：
10.1074/jbc.m806173200
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发表时间：
2009-02-27
影响因子：
4.8
通讯作者：
Claro, Enrique
中科院分区：
文献类型：
--
作者：
Gubern, Albert;Barcelo-Torns, Miquel;Claro, Enrique
本研究探讨了胁迫诱导脂滴（LD）生物合成过程中三酰甘油（TAG）的代谢来源。在没有外部脂肪酸来源的情况下，脂肪酸合成酶的细胞毒性抑制剂诱导CHO-K1细胞中的TAG合成和LD生物合成。TAG合成是LD生物发生所必需的，并且对VIA族磷脂酶A（2）（iPLA（2）-VIA）表达的抑制和下调敏感。用酸性pH、C-2-神经酰胺、衣霉素或葡萄糖剥夺诱导应激也以依赖于iPLA（2）-VIA的方式刺激TAG合成和LD形成。过表达的酶增强TAG合成内源性脂肪酸和LD的发生。在应激期间，LD生物合成而非TAG合成需要IVA PLA（2）（cPLA（2）α）组的磷酸化和活化。结果表明，iPLA（2）-VIA为TAG合成提供脂肪酸，而cPLA（2）α允许LD生物合成。LD在应激过程中的生物合成可能是一种生存策略，将结构磷脂回收到能量产生底物中。
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.