Hydroxysteroid dehydrogenase family proteins on lipid droplets through bacteria, C-elegans, and mammals
Hydroxysteroid dehydrogenase family proteins on lipid droplets through bacteria, C-elegans, and mammals
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细菌、线虫和哺乳动物脂滴上的羟基类固醇脱氢酶家族蛋白
DOI：
10.1016/j.bbalip.2018.04.018
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发表时间：
2018-08-01
影响因子：
4.8
通讯作者：
Liu, Pingsheng
中科院分区：
文献类型：
--
作者：
Liu, Yangli;Xu, Shimeng;Liu, Pingsheng
脂滴（ld）是几乎所有物种（从细菌到人类）的主要脂肪储存部位。在哺乳动物、果蝇和一些黏菌中发现了perilipin家族的LD蛋白，但没有发现含有序列保守的细菌LD蛋白。在这项研究中，我们报道了通过LD蛋白质组学分析在所有生物体的LD上发现了羟基类固醇脱氢酶（HSD）家族。成像实验证实LD靶向3种具有代表性的HSD蛋白，包括RHAl中的ro01416、秀丽隐杆线虫中的DHS-3和人细胞中的17 β - hsd11。在秀丽隐杆线虫中，17个β - hsd11家族蛋白（DHS-3、DHS-4和DHS-19）定位在不同组织的ld上。在秀丽隐杆线虫肠细胞中，DHS-3靶向胞质ld， DHS-9标记核ld。此外，17 β - hsd11家族的n端疏水结构域是其靶向LDs所必需的。最后，17个β - hsd11家族蛋白诱导LD聚集，DHS3缺失导致线虫脂质降低。17个β - hsd11家族蛋白通过影响LD相关的ATGL来调节LD动力学和脂质代谢，这在秀丽隐杆线虫和人类之间是保守的。综上所述，这些研究结果不仅为多种生物中LDs的动力学和功能的机制研究提供了新的视角，而且为理解细胞器的进化史提供了新的视角。
Lipid droplets (LDs) are the main fat storing sites in almost all species from bacteria to humans. The perilipin family has been found as LD proteins in mammals, Drosophila, and a couple of slime molds, but no bacterial LD proteins containing sequence conservation were identified. In this study, we reported that the hydroxysteroid dehydrogenase (HSD) family was found on LDs across all organisms by LD proteomic analysis. Imaging experiments confirmed LD targeting of three representative HSD proteins including ro01416 in RHAl, DHS-3 in C. elegans, and 17 beta-HSD11 in human cells. In C. elegans, 17 beta-HSD11 family proteins (DHS-3, DHS-4 and DHS-19) were localized on LDs in distinct tissues. In intestinal cells of C. elegans, DHS-3 targeted to cytoplasmic LDs, while DHS-9 labeled nuclear LDs. Furthermore, the N-terminal hydrophobic domains of 17 beta-HSD11 family were necessary for their targeting to LDs. Last, 17 beta-HSD11 family proteins induced LD aggregation, and deletion of DHS3 in C. elegans caused lipid decrease. Independent of their presumptive catalytic sites, 17 beta-HSD11 family proteins regulated LD dynamics and lipid metabolism through affecting the LD-associated ATGL, which was conserved between C. elegans and humans. Together, these findings for HSDs provide a new insight not only into the mechanistic studies of the dynamics and functions of LDs in multiple organisms, but also into understanding the evolutionary history of the organelle.