Abstract
SummaryThe inner nuclear membrane (INM) encases the genome and is fused with the outer nuclear membrane (ONM) to form the nuclear envelope. The ONM is contiguous with the endoplasmic reticulum (ER), the main site of phospholipid synthesis. In contrast to the ER and ONM, evidence for a metabolic activity of the INM has been lacking. Here, we show that the INM is an adaptable membrane territory capable of lipid metabolism. S. cerevisiae cells target enzymes to the INM that can promote lipid storage. Lipid storage involves the synthesis of nuclear lipid droplets from the INM and is characterized by lipid exchange through Seipin-dependent membrane bridges. We identify the genetic circuit for nuclear lipid droplet synthesis and a role of these organelles in regulating this circuit by sequestration of a transcription factor. Our findings suggest a link between INM metabolism and genome regulation and have potential relevance for human lipodystrophy.
Highlights
The endoplasmic reticulum (ER) synthesizes phospholipids for membrane growth and cell proliferation, and triacylglycerol (TAG) to store energy (van Meer et al, 2008)
TAGs and steryl esters are stored in lipid droplets, which are synthesized on the ER and outer nuclear membrane (ONM) (Hashemi and Goodman, 2015; Thiam et al, 2013)
Lipid Biosensors for Probing the inner nuclear membrane (INM) The INM and ONM are only 10–50 nm apart and biochemical fractionation fails to separate them into pure fractions that would be suitable for lipidomics (Monneron et al, 1972)
Summary
The endoplasmic reticulum (ER) synthesizes phospholipids for membrane growth and cell proliferation, and triacylglycerol (TAG) to store energy (van Meer et al, 2008). TAG and phospholipids have common precursors, and the flow of lipids into storage or growth is a key cellular decision that is balanced with nutrient availability (Figure 1A). TAGs and steryl esters are stored in lipid droplets, which are synthesized on the ER and outer nuclear membrane (ONM) (Hashemi and Goodman, 2015; Thiam et al, 2013). Lipid droplets have sporadically been observed inside the nucleus of some mammalian cells (Layerenza et al, 2013; Ohsaki et al, 2016; Uzbekov and Roingeard, 2013), lipid droplet synthesis is considered to be the task of the ER/ONM (Figure 1B)
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