Membrane Curvature Catalyzes Lipid Droplet Assembly

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Santinho , A , Salo , V T , Chorlay , A , Li , S , Zhou , X , Omrane , M , Ikonen , E & Thiam , A R 2020 , ' Membrane Curvature Catalyzes Lipid Droplet Assembly ' , Current Biology , vol. 30 , no. 13 , pp. 2481-+ . https://doi.org/10.1016/j.cub.2020.04.066

Title: Membrane Curvature Catalyzes Lipid Droplet Assembly
Author: Santinho, Alexandre; Salo, Veijo T.; Chorlay, Aymeric; Li, Shiqian; Zhou, Xin; Omrane, Mohyeddine; Ikonen, Elina; Thiam, Abdou Rachid
Contributor: University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
Date: 2020-07-06
Language: eng
Number of pages: 20
Belongs to series: Current Biology
ISSN: 0960-9822
URI: http://hdl.handle.net/10138/332254
Abstract: Lipid droplet (LD) biogenesis begins in the endoplasmic reticulum (ER) bilayer, but how the ER topology impacts this process is unclear. An early step in LD formation is nucleation, wherein free neutral lipids, mainly triacylglycerols (TGs) and sterol esters (SEs), condense into a nascent LD. How this transition occurs is poorly known. Here, we found that LDs preferably assemble at ER tubules, with higher curvature than ER sheets, independently of the LD assembly protein seipin. Indeed, the critical TG concentration required for initiating LD assembly is lower at curved versus flat membrane regions. In agreement with this finding, flat ER regions bear higher amounts of free TGs than tubular ones and present less LDs. By using an in vitro approach, we discovered that the presence of free TGs in tubules is energetically unfavorable, leading to outflow of TGs to flat membrane regions or condensation into LDs. Accordingly, in vitro LD nucleation can be achieved by the sole increase of membrane curvature. In contrast to TGs, the presence of free SEs is favored at tubules and increasing SE levels is inhibitory to the curvature-induced nucleation of TG LDs. Finally, we found that seipin is enriched at ER tubules and controls the condensation process, preventing excessive tubule-induced nucleation. The absence of seipin provokes erratic LD nucleation events determined by the abundance of ER tubules. In summary, our data indicate that membrane curvature catalyzes LD assembly.
Subject: ENDOPLASMIC-RETICULUM
ER
SEIPIN
CONTACTS
CELL
LIPODYSTROPHY
BIOGENESIS
DOMAINS
FAMILY
GROWTH
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
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