Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets

Abstract
Data availability
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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

The following data sets were generated

1. Zoni V
2. Khaddaj R
3. Campomanes P
4. Thiam AR
5. Schneiter R
6. Vanni S
(2021) Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets
Zenodo, doi:10.5281/zenodo.4457468.

http://doi.org/10.5281/zenodo.4457468

Article and author information

Author details

Valeria Zoni

Department of Biology, University of Fribourg, Fribourg, Switzerland

Competing interests
The authors declare that no competing interests exist.
Rasha Khaddaj

Department of Biology, University of Fribourg, Fribourg, Switzerland

Competing interests
The authors declare that no competing interests exist.
Pablo Campomanes

Department of Biology, University of Fribourg, Fribourg, Switzerland

Competing interests
The authors declare that no competing interests exist.
Abdou Rachid Thiam

ENS, Université PSL, CNRS, Laboratoire de Physique de l'École Normale Supérieure, Paris, France

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7488-4724
Roger Schneiter

Departemnt of Biology, University of Fribourg, Fribourg, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9102-8396
Stefano Vanni

Department of Biology, University of Fribourg, Fribourg, Switzerland

For correspondence
stefano.vanni@unifr.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2146-1140

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

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.