Obese yeast: Triglyceride lipolysis is functionally conserved from mammals to yeast
Obese yeast: Triglyceride lipolysis is functionally conserved from mammals to yeast
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DOI：
10.1074/jbc.m508414200
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发表时间：
2006-01-06
影响因子：
4.8
通讯作者：
Kohlwein, SD
中科院分区：
文献类型：
--
作者：
Kurat, CF;Natter, K;Kohlwein, SD
甘油三酯的储存和降解是确保能量稳态和膜脂质合成前体可用性的重要过程。最近的证据表明，一类新出现的酶含有一个保守的patatin结构域是重要的球员在脂质降解。在这里，我们描述了一个主要的甘油三酯脂肪酶的脂肪甘油三酯脂肪酶/布鲁默家族，TGL 4，在酵母酿酒酵母的鉴定和表征。在tgl 3背景中消除Tgl 4导致脂肪酵母，使得生长的细胞不能降解甘油三酯。Tgl 4和Tgl 3脂肪酶定位于脂滴，彼此独立。Tgl 4马铃薯糖蛋白结构域的GXSXG脂肪酶活性位点共有序列中的丝氨酸315对于催化活性是必需的。小鼠脂肪甘油三酯脂肪酶（也含有马铃薯糖蛋白结构域，但在其他方面与任何酵母蛋白的一级结构高度不同）在酵母中表达时定位于脂滴，并在体内显著恢复tgl 4突变体中的甘油三酯分解。我们的数据将酵母Tgl 4鉴定为哺乳动物脂肪甘油三酯脂肪酶的功能性直系同源物。
Storage and degradation of triglycerides are essential processes to ensure energy homeostasis and availability of precursors for membrane lipid synthesis. Recent evidence suggests that an emerging class of enzymes containing a conserved patatin domain are centrally important players in lipid degradation. Here we describe the identification and characterization of a major triglyceride lipase of the adipose triglyceride lipase/ Brummer family, Tgl4, in the yeast Saccharomyces cerevisiae. Elimination of Tgl4 in a tgl3 background led to fat yeast, rendering growing cells unable to degrade triglycerides. Tgl4 and Tgl3 lipases localized to lipid droplets, independent of each other. Serine 315 in the GXSXG lipase active site consensus sequence of the patatin domain of Tgl4 is essential for catalytic activity. Mouse adipose triglyceride lipase ( which also contains a patatin domain but is otherwise highly divergent in primary structure from any yeast protein) localized to lipid droplets when expressed in yeast, and significantly restored triglyceride breakdown in tgl4 mutants in vivo. Our data identify yeast Tgl4 as a functional ortholog of mammalian adipose triglyceride lipase.