A role for seipin in lipid droplet dynamics and inheritance in yeast
A role for seipin in lipid droplet dynamics and inheritance in yeast
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DOI：
10.1242/jcs.091454
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发表时间：
2011-11
影响因子：
4
通讯作者：
H. Wolinski;D. Kolb;S. Hermann;R. Koning;S. Kohlwein
中科院分区：
文献类型：
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作者：
H. Wolinski;D. Kolb;S. Hermann;R. Koning;S. Kohlwein
参与细胞脂质储存和动员的过程的功能障碍诱导流行的人类疾病如肥胖症、2型糖尿病和动脉粥样硬化的发病机制。脂滴是真核细胞中中性脂质的主要脂质储存库，并且因此实现平衡细胞脂质代谢和能量稳态的基本功能。尽管在确定参与脂质储存的关键代谢酶及其在各种模式生物中的调节方面取得了重大进展，但关于脂滴的生物发生、亚细胞分布和遗传的一些基本问题尚未解决。在这项研究中，我们应用了一套成像技术，如高分辨率四维（4D）活细胞成像，定量显微镜，透射电子显微镜和电子断层扫描，以深入了解在酵母酿酒酵母细胞生长过程中的脂滴的时空组织。该分析揭示了单个细胞中脂滴的亚细胞定位的高水平组织，它们向细胞外周的定向迁移以及在细胞分裂期间脂滴亚群向子细胞的协调转移。脂滴似乎仍然与ER膜在细胞生长过程中独立的大小和亚细胞定位。FLD 1（编码seipin的人类BSCL 2基因的功能直向同源物）的缺失导致酵母脂滴动力学受损和脂肪分解缺陷，这可能是由于这些突变体中异常的ER结构造成的。我们的数据表明，酵母seipin作为一个脚手架蛋白，需要一个特定的亚结构域的ER的动力学的作用，并提供了一个新的方面的异常脂滴表型的酵母突变体缺乏seipin的解释。
Malfunctions of processes involved in cellular lipid storage and mobilization induce the pathogenesis of prevalent human diseases such as obesity, type 2 diabetes and atherosclerosis. Lipid droplets are the main lipid storage depots for neutral lipids in eukaryotic cells, and as such fulfil an essential function to balance cellular lipid metabolism and energy homeostasis. Despite significant progress in identifying key metabolic enzymes involved in lipid storage and their regulation in various model organisms, some fundamental questions as to the biogenesis, subcellular distribution and inheritance of lipid droplets are as yet unsolved. In this study, we applied a set of imaging techniques such as high-resolution four-dimensional (4D) live-cell imaging, quantitative microscopy, transmission electron microscopy and electron tomography to gain insight into the spatio-temporal organization of lipid droplets during cellular growth in the yeast Saccharomyces cerevisiae. This analysis revealed a high level of organization of the subcellular positioning of lipid droplets in individual cells, their directed migration towards the cellular periphery and a coordinated transfer of a subpopulation of lipid droplets into daughter cells during cell division. Lipid droplets appear to remain associated with ER membranes during cellular growth independently of their size and subcellular localization. Deletion of FLD1, the functional orthologue of the human BSCL2 gene encoding seipin, leads to impaired dynamics of yeast lipid droplets and defective lipolysis, which might be due to aberrant ER structures in these mutants. Our data suggest a role for yeast seipin as a scaffolding protein that is required for the dynamics of a specific subdomain of the ER, and provide a new aspect for the interpretation of abnormal lipid droplets phenotypes in yeast mutants lacking seipin.