Repository logo
 

Lipid partitioning at the nuclear envelope controls membrane biogenesis.


Change log

Authors

Barbosa, Antonio Daniel 
Sembongi, Hiroshi 
Su, Wen-Min 
Abreu, Susana 
Reggiori, Fulvio 

Abstract

Partitioning of lipid precursors between membranes and storage is crucial for cell growth, and its disruption underlies pathologies such as cancer, obesity, and type 2 diabetes. However, the mechanisms and signals that regulate this process are largely unknown. In yeast, lipid precursors are mainly used for phospholipid synthesis in nutrient-rich conditions in order to sustain rapid proliferation but are redirected to triacylglycerol (TAG) stored in lipid droplets during starvation. Here we investigate how cells reprogram lipid metabolism in the endoplasmic reticulum. We show that the conserved phosphatidate (PA) phosphatase Pah1, which generates diacylglycerol from PA, targets a nuclear membrane subdomain that is in contact with growing lipid droplets and mediates TAG synthesis. We find that cytosol acidification activates the master regulator of Pah1, the Nem1-Spo7 complex, thus linking Pah1 activity to cellular metabolic status. In the absence of TAG storage capacity, Pah1 still binds the nuclear membrane, but lipid precursors are redirected toward phospholipids, resulting in nuclear deformation and a proliferation of endoplasmic reticulum membrane. We propose that, in response to growth signals, activation of Pah1 at the nuclear envelope acts as a switch to control the balance between membrane biogenesis and lipid storage.

Description

Keywords

Endoplasmic Reticulum, Lipid Droplets, Lipid Metabolism, Membrane Lipids, Membranes, Nuclear Envelope, Nuclear Proteins, Phosphatidate Phosphatase, Phospholipids, Saccharomyces cerevisiae Proteins, Triglycerides

Journal Title

Mol Biol Cell

Conference Name

Journal ISSN

1059-1524
1939-4586

Volume Title

26

Publisher

American Society for Cell Biology (ASCB)
Sponsorship
Medical Research Council (G0701446)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (093026/Z/10/Z)
This work was supported by grants from the Medical Research Council (G0701446) to S.S; a Wellcome Trust Strategic Award (100140) and equipment grant (093026) to the Cambridge Institute for Medical Research; the National Institutes of Health (GM050679) to G.M.C.; a ALW Open Program (822.02.014), DFG-NWO cooperation (DN82-303), SNSF Sinergia (CRSII3_154421) and ZonMW VICI (016.130.606) grants to F.R; and a PhD fellowship from the Fundação para a Ciência e a Tecnologia (FCT) to S.A.