Zhang Qian, Chieu Hai Kee, Low Choon Pei, Zhang Shaochong, Heng Chew Kiat, Yang Hongyuan
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore 119260, Republic of Singapore.
J Biol Chem. 2003 Nov 21;278(47):47145-55. doi: 10.1074/jbc.M306998200. Epub 2003 Sep 8.
Triacylglycerols (TAG) are important energy storage molecules for nearly all eukaryotic organisms. In this study, we found that two gene products (Plh1p and Dga1p) are responsible for the terminal step of TAG synthesis in the fission yeast Schizosaccharomyces pombe through two different mechanisms: Plh1p is a phospholipid diacylglycerol acyltransferase, whereas Dga1p is an acyl-CoA:diacylglycerol acyltransferase. Cells with both dga1+ and plh1+ deleted (DKO cells) lost viability upon entry into the stationary phase and demonstrated prominent apoptotic markers. Exponentially growing DKO cells also underwent dramatic apoptosis when briefly treated with diacylglycerols (DAGs) or free fatty acids. We provide strong evidence suggesting that DAG, not sphingolipids, mediates fatty acids-induced lipoapoptosis in yeast. Lastly, we show that generation of reactive oxygen species is essential to lipoapoptosis.
三酰甘油(TAG)是几乎所有真核生物重要的能量储存分子。在本研究中,我们发现裂殖酵母粟酒裂殖酵母中,两种基因产物(Plh1p和Dga1p)通过两种不同机制负责TAG合成的终末步骤:Plh1p是一种磷脂二酰甘油酰基转移酶,而Dga1p是一种酰基辅酶A:二酰甘油酰基转移酶。同时缺失dga1+和plh1+的细胞(DKO细胞)进入稳定期后失去活力,并表现出明显的凋亡标志物。指数生长的DKO细胞在用二酰甘油(DAG)或游离脂肪酸短暂处理后也会发生显著凋亡。我们提供了有力证据表明,介导酵母中脂肪酸诱导的脂质凋亡的是DAG,而非鞘脂。最后,我们表明活性氧的产生对脂质凋亡至关重要。