Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets
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
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
-
- 3,032
- views
-
- 545
- downloads
-
- 74
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Cell Biology
Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify 14 EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A Piezo2+ population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic, and pharmacological approaches, we demonstrated Piezo2+ ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.
-
- Cell Biology
- Developmental Biology
A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.