期刊
MOLECULAR BIOLOGY OF THE CELL
卷 26, 期 20, 页码 3641-3657出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E15-03-0173
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资金
- Medical Research Council [G0701446]
- Wellcome Trust [100140, 093026]
- National Institutes of Health [GM050679]
- ALW Open Programme [822.02.014]
- Deutsche Forschungsgemeinschaft-Netherlands Organisation for Scientific Research Cooperation [DN82-303]
- Swiss National Science Foundation Sinergia [CRSII3_154421]
- ZonMW VICI [016.130.606]
- Fundacao para a Ciencia e a Tecnologia
- MRC [G0701446] Funding Source: UKRI
- Swiss National Science Foundation (SNF) [CRSII3_154421] Funding Source: Swiss National Science Foundation (SNF)
- Medical Research Council [G0701446] Funding Source: researchfish
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.
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