School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
PLoS Genet. 2011 Jul;7(7):e1002201. doi: 10.1371/journal.pgen.1002201. Epub 2011 Jul 28.
Lipid droplets (LDs) are important cellular organelles that govern the storage and turnover of lipids. Little is known about how the size of LDs is controlled, although LDs of diverse sizes have been observed in different tissues and under different (patho)physiological conditions. Recent studies have indicated that the size of LDs may influence adipogenesis, the rate of lipolysis and the oxidation of fatty acids. Here, a genome-wide screen identifies ten yeast mutants producing "supersized" LDs that are up to 50 times the volume of those in wild-type cells. The mutated genes include: FLD1, which encodes a homologue of mammalian seipin; five genes (CDS1, INO2, INO4, CHO2, and OPI3) that are known to regulate phospholipid metabolism; two genes (CKB1 and CKB2) encoding subunits of the casein kinase 2; and two genes (MRPS35 and RTC2) of unknown function. Biochemical and genetic analyses reveal that a common feature of these mutants is an increase in the level of cellular phosphatidic acid (PA). Results from in vivo and in vitro analyses indicate that PA may facilitate the coalescence of contacting LDs, resulting in the formation of "supersized" LDs. In summary, our results provide important insights into how the size of LDs is determined and identify novel gene products that regulate phospholipid metabolism.
脂滴（LDs）是重要的细胞细胞器，负责脂质的储存和周转。尽管在不同的组织和不同的（病理）生理条件下观察到了不同大小的 LD，但对于 LD 的大小如何受到控制却知之甚少。最近的研究表明，LD 的大小可能会影响脂肪生成、脂肪分解的速度和脂肪酸的氧化。在这里，全基因组筛选确定了十个产生“超大”LD 的酵母突变体，其大小是野生型细胞中 LD 的 50 倍。突变的基因包括：编码哺乳动物 seipin 同源物的 FLD1；五个已知调节磷脂代谢的基因（CDS1、INO2、INO4、CHO2 和 OPI3）；编码酪蛋白激酶 2 亚基的两个基因（CKB1 和 CKB2）；以及两个功能未知的基因（MRPS35 和 RTC2）。生化和遗传分析表明，这些突变体的一个共同特征是细胞磷脂酸（PA）水平的增加。体内和体外分析的结果表明，PA 可能促进接触的 LD 的合并，导致“超大”LD 的形成。总之，我们的结果提供了关于 LD 大小如何确定的重要见解，并确定了调节磷脂代谢的新基因产物。
