@article{e25c11001c834def8432856a6aaff85c,
title = "Compartmentalized Synthesis of Triacylglycerol at the Inner Nuclear Membrane Regulates Nuclear Organization",
abstract = "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.",
author = "Barbosa, {Antonio D.} and Koini Lim and Muriel Mari and Edgar, {James R.} and Lihi Gal and Peter Sterk and Jenkins, {Benjamin J.} and Albert Koulman and Savage, {David B.} and Maya Schuldiner and Fulvio Reggiori and Wigge, {Philip A.} and Symeon Siniossoglou",
note = "We thank Nicholas Ktistakis, Delphine Larrieu, Helena Santos-Rosa, and Alison Schuldt for comments on the manuscript; Andrew Peden and Liesbeth Veenhoff for reagents; Matthew Gratian and Mark Bowen for help with microscopy; and Reiner Schulte and Chiara Cossetti for help with FACS analysis. This work was supported by a Wellcome Trust Seed award (108042) to S.S.; a Wellcome Trust Strategic award (100140) and an equipment grant (093026) to the Cambridge Institute for Medical Research; a Wellcome Trust Senior fellowship to D.B.S. (WT 107064); a Marie Sk{\l}odowska-Curie Cofund (713660), a Marie Sk{\l}odowska-Curie ITN (765912), a ALW Open Program (ALWOP.310), and ZonMW VICI grant (016.130.606) to F.R.; a ALW Open Program grant (ALWOP.355) to M.M.; a BBSRC grant (BB/M027252/1) to A.K.; a Volkswagen “Life” grant to M.S.; and a fellowship from the Gatsby Foundation (GAT3273/GLB) to P.A.W. J.R.E. was supported by Wellcome Trust (grant 086598). M.S. is an incumbent of the Dr. Gilbert Omenn and Martha Darling Professorial Chair in Molecular Genetics. Author Contributions Conceptualization, S.S.; Experimental design, S.S., A.D.B., and P.A.W.; Yeast experimental work, A.D.B. and S.S.; Electron microscopy, M.M., J.R.E., and F.R.; FRAP and live microscopy, K.L. and D.B.S.; High-content imaging screen, M.S., L.G., and A.D.B.; Yeast lipid profiling, B.J.J. and A.K.; Bioinformatics, P.S.; Data analysis, S.S. and A.D.B. with the help of the other authors; Writing, S.S. and A.D.B.; Review/editing, all authors.",
year = "2019",
month = sep,
day = "23",
doi = "https://doi.org/10.1016/j.devcel.2019.07.009",
language = "الإنجليزيّة",
volume = "50",
pages = "755--766",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "6",
}