Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets
- University of Fribourg, Switzerland
- Laboratoire de Physique de l'École Normale Supérieure, France
Abstract
Cells store energy in the form of neutral lipids packaged into micrometer-sized organelles named lipid droplets (LD). These structures emerge from the endoplasmic reticulum (ER) at sites marked by the protein seipin, but the mechanisms regulating their biogenesis remain poorly understood. Using a combination of molecular simulations, yeast genetics and fluorescence microscopy, we show that interactions between lipids' acyl-chains modulate the propensity of neutral lipids to be stored in LD, in turn preventing or promoting their accumulation in the ER membrane. Our data suggest that diacylglycerol, that is enriched at sites of LD formation, promotes the packaging of neutral lipids into LDs, together with ER-abundant lipids, such as phosphatidylethanolamine. On the opposite end, short and saturated acyl-chains antagonize fat storage in LD and promote accumulation of neutral lipids in the ER. Our results provide a new conceptual understanding of LD biogenesis in the context of ER homeostasis and function.
Data availability
Data Availability: All source data, input files for MD simulations and statistical analyses can be found at the following DOI: http://doi.org/10.5281/zenodo.4457468
-
Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid dropletsZenodo, doi:10.5281/zenodo.4457468.
Article and author information
Author details
Abdou Rachid Thiam
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (163966)
- Valeria Zoni
- Pablo Campomanes
- Stefano Vanni
Novartis Stiftung für Medizinisch-Biologische Forschung (19B140)
- Roger Schneiter
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_17303)
- Roger Schneiter
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Zoni et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,832
- views
-
- 520
- downloads
-
- 64
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets
eLife 10:e62886.
https://doi.org/10.7554/eLife.62886
Further reading
-
- Cell Biology
- Developmental Biology
The formation of large endolysosomal structures in unfertilized eggs ensures that lysosomes remain dormant before fertilization, and then shift into clean-up mode after the egg-to-embryo transition.
-
- Cell Biology
- Developmental Biology
During Caenorhabditis elegans development, multiple cells migrate long distances or extend processes to reach their final position and/or attain proper shape. The Wnt signalling pathway stands out as one of the major coordinators of cell migration or cell outgrowth along the anterior-posterior body axis. The outcome of Wnt signalling is fine-tuned by various mechanisms including endocytosis. In this study, we show that SEL-5, the C. elegans orthologue of mammalian AP2-associated kinase AAK1, acts together with the retromer complex as a positive regulator of EGL-20/Wnt signalling during the migration of QL neuroblast daughter cells. At the same time, SEL-5 in cooperation with the retromer complex is also required during excretory canal cell outgrowth. Importantly, SEL-5 kinase activity is not required for its role in neuronal migration or excretory cell outgrowth, and neither of these processes is dependent on DPY-23/AP2M1 phosphorylation. We further establish that the Wnt proteins CWN-1 and CWN-2, together with the Frizzled receptor CFZ-2, positively regulate excretory cell outgrowth, while LIN-44/Wnt and LIN-17/Frizzled together generate a stop signal inhibiting its extension.
