Retinyl esters form lipid droplets independently of triacylglycerol and seipin

Martijn R Molenaar; Kamlesh K Yadav; Alexandre Toulmay; Tsjerk A Wassenaar; Muriel C Mari; Lucie Caillon; Aymeric Chorlay; Ivan E Lukmantara; Maya W Haaker; Richard W Wubbolts; Martin Houweling; Arie Bas Vaandrager; Xavier Prieur; Fulvio Reggiori; Vineet Choudhary; Hongyuan Yang; Roger Schneiter; Abdou Rachid Thiam; William A Prinz; J Bernd Helms

doi:10.1083/jcb.202011071

Retinyl esters form lipid droplets independently of triacylglycerol and seipin

Martijn R Molenaar, Kamlesh K Yadav, Alexandre Toulmay, Tsjerk A Wassenaar, Muriel C Mari, Lucie Caillon, Aymeric Chorlay, Ivan E Lukmantara, Maya W Haaker, Richard W Wubbolts, Martin Houweling, Arie Bas Vaandrager, Xavier Prieur, Fulvio Reggiori, Vineet Choudhary, Hongyuan Yang, Roger Schneiter, Abdou Rachid Thiam, William A Prinz, J Bernd Helms

National Institutes of Health
University of Groningen, University Medical Center Groningen, Department of Paediatric Pulmonology and Paediatric Allergology, Beatrix Children's Hospital, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
Institut de Biologie de l'Ecole Normale Supérieure, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8197, Institut National de la Santé et de la Recherche Médicale U1024, Ecole Normale Supérieure, Paris Sciences et Lettres Research University, F-75005, France.
Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Université de Nantes
University of Fribourg

Research output: Contribution to journal › Article › Academic › peer-review

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 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.

Original language	English
Article number	e202011071
Pages (from-to)	1-14
Journal	Journal of Cell Biology
Volume	220
Issue number	10
DOIs	https://doi.org/10.1083/jcb.202011071
Publication status	Published - 4 Oct 2021

Bibliographical 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.

Keywords

Biochemistry
Biophysics
Organelles

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jcb_202011071Final published version, 5.34 MBLicence: CC BY

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Molenaar, M. R., Yadav, K. K., Toulmay, A., Wassenaar, T. A., Mari, M. C., Caillon, L., Chorlay, A., Lukmantara, I. E., Haaker, M. W., Wubbolts, R. W., Houweling, M., Vaandrager, A. B., Prieur, X., Reggiori, F., Choudhary, V., Yang, H., Schneiter, R., Thiam, A. R., Prinz, W. A., & Helms, J. B. (2021). Retinyl esters form lipid droplets independently of triacylglycerol and seipin. Journal of Cell Biology, 220(10), 1-14. Article e202011071. https://doi.org/10.1083/jcb.202011071

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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 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.",

keywords = "Biochemistry, Biophysics, Organelles",

author = "Molenaar, {Martijn R} and Yadav, {Kamlesh K} and Alexandre Toulmay and Wassenaar, {Tsjerk A} and Mari, {Muriel C} and Lucie Caillon and Aymeric Chorlay and Lukmantara, {Ivan E} and Haaker, {Maya W} and Wubbolts, {Richard W} and Martin Houweling and Vaandrager, {Arie Bas} and Xavier Prieur and Fulvio Reggiori and Vineet Choudhary and Hongyuan Yang and Roger Schneiter and Thiam, {Abdou Rachid} and Prinz, {William A} and Helms, {J Bernd}",

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: {\textcopyright} 2021 Crown copyright.",

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doi = "10.1083/jcb.202011071",

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Molenaar, MR, Yadav, KK, Toulmay, A, Wassenaar, TA, Mari, MC, Caillon, L, Chorlay, A, Lukmantara, IE, Haaker, MW , Wubbolts, RW , Houweling, M , Vaandrager, AB, Prieur, X, Reggiori, F, Choudhary, V, Yang, H, Schneiter, R, Thiam, AR, Prinz, WA & Helms, JB 2021, 'Retinyl esters form lipid droplets independently of triacylglycerol and seipin', Journal of Cell Biology, vol. 220, no. 10, e202011071, pp. 1-14. https://doi.org/10.1083/jcb.202011071

TY - JOUR

T1 - Retinyl esters form lipid droplets independently of triacylglycerol and seipin

AU - Molenaar, Martijn R

AU - Yadav, Kamlesh K

AU - Toulmay, Alexandre

AU - Wassenaar, Tsjerk A

AU - Mari, Muriel C

AU - Caillon, Lucie

AU - Chorlay, Aymeric

AU - Lukmantara, Ivan E

AU - Haaker, Maya W

AU - Wubbolts, Richard W

AU - Houweling, Martin

AU - Vaandrager, Arie Bas

AU - Prieur, Xavier

AU - Reggiori, Fulvio

AU - Choudhary, Vineet

AU - Yang, Hongyuan

AU - Schneiter, Roger

AU - Thiam, Abdou Rachid

AU - Prinz, William A

AU - Helms, J Bernd

N1 - 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.

PY - 2021/10/4

Y1 - 2021/10/4

N2 - 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 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.

AB - 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 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.

KW - Biochemistry

KW - Biophysics

KW - Organelles

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U2 - 10.1083/jcb.202011071

DO - 10.1083/jcb.202011071

M3 - Article

C2 - 34323918

SN - 0021-9525

VL - 220

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EP - 14

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 10

M1 - e202011071

ER -

Retinyl esters form lipid droplets independently of triacylglycerol and seipin

Abstract

Bibliographical note

Keywords

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