Lipid Droplets Are a Physiological Nucleoporin Reservoir
Open Access
- 22 February 2021
- Vol. 10 (2), 472
- https://doi.org/10.3390/cells10020472
Abstract
Lipid Droplets (LD) are dynamic organelles that originate in the Endoplasmic Reticulum and mostly bud off toward the cytoplasm, where they store neutral lipids for energy and protection purposes. LD also have diverse proteins on their surface, many of which are necessary for the their correct homeostasis. However, these organelles also act as reservoirs of proteins that can be made available elsewhere in the cell. In this sense, they act as sinks that titrate key regulators of many cellular processes. Among the specialized factors that reside on cytoplasmic LD are proteins destined for functions in the nucleus, but little is known about them and their impact on nuclear processes. By screening for nuclear proteins in publicly available LD proteomes, we found that they contain a subset of nucleoporins from the Nuclear Pore Complex (NPC). Exploring this, we demonstrate that LD act as a physiological reservoir, for nucleoporins, that impacts the conformation of NPCs and hence their function in nucleo-cytoplasmic transport, chromatin configuration, and genome stability. Furthermore, our in silico modeling predicts a role for LD-released fatty acids in regulating the transit of nucleoporins from LD through the cytoplasm and to nuclear pores.Keywords
Funding Information
- Institut National Du Cancer (SIRIC Montpellier INCa_Inserm_DGOS_12553, FATidic PLBIO19-098 INCA_13832)
- Centre National de la Recherche Scientifique (ATIP-Avenir)
- undefined <span style="color:gray;font-size:10px;">undefined</span> (La Ligue contre le Cancer)
- Merck Sharp and Dohme (GnoSTic)
This publication has 104 references indexed in Scilit:
- Structure and nucleic acid binding activity of the nucleoporin Nup157Proceedings of the National Academy of Sciences, 2013
- Balancing the fat: lipid droplets and human diseaseEMBO Molecular Medicine, 2013
- Dimerization and direct membrane interaction of Nup53 contribute to nuclear pore complex assemblyThe EMBO Journal, 2012
- Lipid particles/droplets of the yeast Saccharomyces cerevisiae revisited: Lipidome meets ProteomeBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2011
- The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic α-helixProceedings of the National Academy of Sciences, 2009
- Sterol and Diacylglycerol Acyltransferase Deficiency Triggers Fatty Acid-mediated Cell DeathJournal of Biological Chemistry, 2009
- Role for perinuclear chromosome tethering in maintenance of genome stabilityNature, 2008
- Crystal Structure of Nucleoporin Nic96 Reveals a Novel, Intricate Helical Domain ArchitectureJournal of Biological Chemistry, 2007
- The Lipid-Droplet Proteome Reveals that Droplets Are a Protein-Storage DepotCurrent Biology, 2006
- The Yeast Nuclear Pore ComplexThe Journal of cell biology, 2000