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

Liu, Y, Xu, S, Zhang, C, Zhu, X, Hammad, MA, Zhang, X, Christian, M ORCID: https://orcid.org/0000-0002-1616-4179, Zhang, H and Liu, P, 2018. Hydroxysteroid dehydrogenase family proteins on lipid droplets through bacteria, C. elegans, and mammals. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1863 (8), pp. 881-894. ISSN 1388-1981

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Abstract

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 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.

Item Type:	Journal article
Publication Title:	Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Creators:	Liu, Y., Xu, S., Zhang, C., Zhu, X., Hammad, M.A., Zhang, X., Christian, M., Zhang, H. and Liu, P.
Publisher:	Elsevier
Date:	August 2018
Volume:	1863
Number:	8
ISSN:	1388-1981
Identifiers:	Number Type 10.1016/j.bbalip.2018.04.018 DOI S1388198118300830 Publisher Item Identifier
Rights:	Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	12 Aug 2019 10:52
Last Modified:	12 Aug 2019 10:52
URI:	https://irep.ntu.ac.uk/id/eprint/37222

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