Increase in cellular triacylglycerol content and emergence of large ER-associated lipid droplets in the absence of CDP-DG synthase function
Increase in cellular triacylglycerol content and emergence of large ER-associated lipid droplets in the absence of CDP-DG synthase function
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DOI：
10.1091/mbc.e14-03-0832
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发表时间：
2014-12-15
影响因子：
3.3
通讯作者：
Oliferenko, Snezhana
中科院分区：
文献类型：
--
作者：
He, Yue;Yam, Candice;Oliferenko, Snezhana
过量的脂肪酸和甾醇以三酰甘油和甾醇酯的形式储存在特殊的细胞器中，称为脂滴。了解是什么决定了中性脂类的细胞量以及它们包装成脂滴的原因，这具有重要的基础和应用价值。使用两种分裂酵母，我们发现缺乏内质网驻留的CDP-DG合成酶CDS1功能的循环细胞表现出显著的三酰甘油含量增加，并聚集与内质网膜密切相关的大脂滴。我们证明，这些不寻常的结构招募了三酰甘油合成机器，并通过膨胀而不是融合来生长。我们的结果表明，干扰磷脂酸利用的CDP-DG途径，重新连接细胞代谢，采取依赖于肯尼迪途径的富含三酰甘油的生活方式。
Excess fatty acids and sterols are stored as triacylglycerols and sterol esters in specialized cellular organelles, called lipid droplets. Understanding what determines the cellular amount of neutral lipids and their packaging into lipid droplets is of fundamental and applied interest. Using two species of fission yeast, we show that cycling cells deficient in the function of the ER-resident CDP-DG synthase Cds1 exhibit markedly increased triacylglycerol content and assemble large lipid droplets closely associated with the ER membranes. We demonstrate that these unusual structures recruit the triacylglycerol synthesis machinery and grow by expansion rather than by fusion. Our results suggest that interfering with the CDP-DG route of phosphatidic acid utilization rewires cellular metabolism to adopt a triacylglycerol-rich lifestyle reliant on the Kennedy pathway.