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
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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.
Reviewing Editor
- Patricia Bassereau, Institut Curie, France
Version history
- Received: September 7, 2020
- Accepted: January 31, 2021
- Accepted Manuscript published: February 1, 2021 (version 1)
- Version of Record published: February 19, 2021 (version 2)
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.
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Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets
eLife 10:e62886.
https://doi.org/10.7554/eLife.62886
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