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Compartmentalized Synthesis of Triacylglycerol at the Inner Nuclear Membrane Regulates Nuclear Organization

Cells dynamically adjust organelle organization in response to growth and environmental cues. This requires regulation of synthesis of phospholipids, the building blocks of organelle membranes, or remodeling of their fatty-acyl (FA) composition. FAs are also the main components of triacyglycerols (TGs), which enable energy storage in lipid droplets. How cells coordinate FA metabolism with organelle biogenesis during cell growth remains unclear. Here, we show that Lro1, an acyltransferase that generates TGs from phospholipid-derived FAs in yeast, relocates from the endoplasmic reticulum to a subdomain of the inner nuclear membrane. Lro1 nuclear targeting is regulated by cell cycle and nutrient starvation signals and is inhibited when the nucleus expands. Lro1 is active at this nuclear subdomain, and its compartmentalization is critical for nuclear integrity. These data suggest that Lro1 nuclear targeting provides a site of TG synthesis, which is coupled with nuclear membrane remodeling.

Barbosa, A.D.; Lim, K.; Mari, M.; Edgar, J.R.; Gal, L.; Sterk, P.; Jenkins, B.J.; Koulman, A; Savage, D.B.; Schuldiner, M.; Reggiori, F.; Wigge, P.A.; Siniossoglou, S. 2019. Compartmentalized synthesis of Triacylglycerol at the inner nuclear membrane regulates nuclear organization. Developmental Cell 50(6), 755-766.

DOI: 10.1016/j.devcel.2019.07.009