Sir William Dunn School of Pathology, University of Oxford, Oxford, England, UK.
Cell and Developmental Biology Programme, Centre for Genomic Regulation, Barcelona, Spain.
J Cell Biol. 2018 Jan 2;217(1):127-138. doi: 10.1083/jcb.201704115. Epub 2017 Nov 29.
Storage and consumption of neutral lipids in lipid droplets (LDs) are essential for energy homeostasis and tightly coupled to cellular metabolism. However, how metabolic cues are integrated in the life cycle of LDs is unclear. In this study, we characterize the function of Ldo16 and Ldo45, two splicing isoforms of the same protein in budding yeast. We show that Ldo proteins interact with the seipin complex, which regulates contacts between LDs and the endoplasmic reticulum (ER). Moreover, we show that the levels of Ldo16 and Ldo45 depend on the growth stage of cells and that deregulation of their relative abundance alters LD morphology, protein localization, and triglyceride content. Finally, we show that absence of Ldo proteins results in defects in LD morphology and consumption by lipophagy. Our findings support a model in which Ldo proteins modulate the activity of the seipin complex, thereby affecting LD properties. Moreover, we identify ER-LD contacts as regulatory targets coupling energy storage to cellular metabolism.
脂滴 (LDs) 中中性脂质的储存和消耗对于能量平衡至关重要，并且与细胞代谢紧密相关。然而，代谢信号如何整合到 LDs 的生命周期中尚不清楚。在这项研究中，我们对芽殖酵母中同一种蛋白质的两种剪接异构体 Ldo16 和 Ldo45 的功能进行了表征。我们发现 Ldo 蛋白与 seipin 复合物相互作用，该复合物调节 LDs 与内质网 (ER) 之间的接触。此外，我们发现 Ldo16 和 Ldo45 的水平取决于细胞的生长阶段，并且它们相对丰度的失调会改变 LD 的形态、蛋白质定位和三酰甘油含量。最后，我们发现 Ldo 蛋白的缺失会导致 LD 形态和通过脂自噬消耗的缺陷。我们的发现支持这样一种模型，即 Ldo 蛋白调节 seipin 复合物的活性，从而影响 LD 的特性。此外，我们确定 ER-LD 接触是将能量储存与细胞代谢相耦合的调节靶点。
