Hydroxysteroid dehydrogenase family proteins on lipid droplets through bacteria, C. elegans , and mammals

Yangli Liu, Shimeng Xu, Congyan Zhang, Xiaotong Zhu, Mirza Ahmed Hammad, Xuelin Zhang, Mark Christian, Hong Zhang, Pingsheng Liu
2018 Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids  
A B S T R A C T 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
more » ... tative HSD proteins including ro01416 in RHA1, DHS-3 in C. elegans, and 17β-HSD11 in human cells. In C. elegans, 17β-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 17β-HSD11 family were necessary for their targeting to LDs. Last, 17β-HSD11 family proteins induced LD aggregation, and deletion of DHS-3 in C. elegans caused lipid decrease. Independent of their presumptive catalytic sites, 17β-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. transport, membrane trafficking, and chaperone function [13] [14] [15] [16] . The protein composition varies among subpopulations of LDs within a cell, or between LDs isolated from different cell types. The best known examples of LD resident proteins are the perilipins. They have been proposed to serve structural roles on the LD surface and have been found to regulate cellular lipid metabolism and play significant roles in human health [17, 18] . Perilipins were first identified in mammals. Their homologs were subsequently found in Drosophila and a few slime molds such as Dictyostelium based on sequence homology [17, 19, 20] . However, similar bioinformatic approaches failed to identify perilipin homologs in other organisms including C. elegans, plants, yeast and bacteria. This raises the question on the existence of evolutionarily conserved LD proteins that are present from bacteria to humans. Using newly developed techniques, LDs have been isolated from many cell types and tissues of almost all model biological organisms and analyzed by proteomic techniques [5, 11, 21, 22] . These studies https://doi.
doi:10.1016/j.bbalip.2018.04.018 pmid:29702244 fatcat:qilbc5dtufex3duffqkgmhbgtu