Retinyl esters form lipid droplets independently of triacylglycerol and seipin
Molenaar, Martijn R; Yadav, Kamlesh K; Toulmay, Alexandre; Wassenaar, Tsjerk A; Mari, Muriel C; Caillon, Lucie; Chorlay, Aymeric; Lukmantara, Ivan E; Haaker, Maya W; Wubbolts, Richard W; Houweling, Martin; Vaandrager, Arie Bas; Prieur, Xavier; Reggiori, Fulvio; Choudhary, Vineet; Yang, Hongyuan; Schneiter, Roger; Thiam, Abdou Rachid; Prinz, William A; Helms, J Bernd
(2021) Journal of Cell Biology, volume 220, issue 10, pp. 1 - 14
(Article)
Abstract
Lipid droplets store neutral lipids, primarily triacylglycerol and steryl esters. Seipin plays a role in lipid droplet biogenesis and is thought to determine the site of lipid droplet biogenesis and the size of newly formed lipid droplets. Here we show a seipin-independent pathway of lipid droplet biogenesis. In silico and
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in vitro experiments reveal that retinyl esters have the intrinsic propensity to sequester and nucleate in lipid bilayers. Production of retinyl esters in mammalian and yeast cells that do not normally produce retinyl esters causes the formation of lipid droplets, even in a yeast strain that produces only retinyl esters and no other neutral lipids. Seipin does not determine the size or biogenesis site of lipid droplets composed of only retinyl esters or steryl esters. These findings indicate that the role of seipin in lipid droplet biogenesis depends on the type of neutral lipid stored in forming droplets.
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Keywords: Biochemistry, Biophysics, Organelles, Cell Biology
ISSN: 0021-9525
Publisher: Rockefeller University Press
Note: Funding Information: This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. H. Yang is supported by project grants from the National Health and Medical Research Council (1141938, 1141939, and 1144726). The authors declare no competing financial interests. Funding Information: We thank Shreyas Sinha and Elmon Meijering for their assistance during the initial phase of experiments. Microscopic im-ages were acquired at the Center of Cellular Imaging, Faculty of Veterinary Medicine, Utrecht University. We thank Esther van?t Veld for technical assistance. Lipid analyses were performed at the Lipidomics Centre, Faculty of Veterinary Medicine, Utrecht University. We thank Jeroen Jansen for technical assistance. EM for quantification of LD size in yeast (Fig. 4) was performed at the Electron Microscopy Core Facility at the University of Texas Southwestern Medical Center. We thank Alain de Bruin, Simon de Neck, and Elsbeth van Liere at the Dutch Molecular Pathology Center (Utrecht University) for expert help and analysis of sei-pin KO livers. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. H. Yang is supported by project grants from the National Health and Medical Research Council (1141938, 1141939, and 1144726). Publisher Copyright: © 2021 Crown copyright.
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