@article{55e01dcdcb744f3bbaa6da8f693123d5,
title = "Diacylglycerol at the inner nuclear membrane fuels nuclear envelope expansion in closed mitosis",
abstract = "Nuclear envelope (NE) expansion must be controlled to maintain nuclear shape and function. The nuclear membrane expands massively during closed mitosis, enabling chromosome segregation within an intact NE. Phosphatidic acid (PA) and diacylglycerol (DG) can both serve as biosynthetic precursors for membrane lipid synthesis. How they are regulated in time and space and what the implications are of changes in their flux for mitotic fidelity are largely unknown. Using genetically encoded PA andDGprobes,we show that DG is depleted from the inner nuclear membrane during mitosis in the fission yeast Schizosaccharomyces pombe, but PA does not accumulate, indicating that it is rerouted to membrane synthesis. We demonstrate that DG-to-PA conversion catalyzed by the diacylglycerol kinase Dgk1 (also known as Ptp4) and direct glycerophospholipid synthesis from DG by diacylglycerol cholinephosphotransferase/ ethanolaminephosphotransferase Ept1 reinforce NE expansion. We conclude that DG consumption through both the de novo pathway and the Kennedy pathway fuels a spike in glycerophospholipid biosynthesis, controlling NE expansion and, ultimately, mitotic fidelity.",
keywords = "Nuclear Envelope, Lipid Metabolism, Diacylglycerol, CLOSED MITOSIS",
author = "Sherman Foo and Amaury Cazenave-Gassiot and Markus Wenk and Snezhana Oliferenko",
note = "Funding Information: We are grateful to the Oliferenko laboratory for discussions and Eugene Makeyev for suggestions on the manuscript. We thank Lydia Thompson and the Crick Flow Cytometry STP for help with FACS experiments, and Foo Juat Chin and the Singapore Lipidomics Incubator laboratory members for help with lipidomics experiments. Work in the S.O. laboratory was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC0102), the UK Medical Research Council (CC0102) and the Wellcome Trust (CC0102). Funding Information: S.F. was in part supported by a King{\textquoteright}s College London–National University of Singapore joint PhD scholarship. Work in the M.R.W. laboratory is supported by grants from the National University of Singapore via the Life Sciences Institute, the National Research Foundation Singapore (NRFSBP-P4) and the National Research Foundation Singapore and Agency for Science, Technology and Research Industry Alignment Fund–Industry Collaboration Project (IAF-ICP) grant I1901E0040. Work in the S.O. laboratory was supported by the Francis Crick Institute, a Wellcome Trust Senior Investigator Award (103741/Z/14/Z), a Wellcome Trust Investigator Award in Science (220790/Z/20/Z) and a Biotechnology and Biological Sciences Research Council grant (BB/T000481/1) to S.O. Open access funding provided by The Francis Crick Institute. Deposited in PMC for immediate release. Publisher Copyright: {\textcopyright} 2023. Published by The Company of Biologists Ltd.",
year = "2023",
month = feb,
day = "2",
doi = "10.1242/jcs.260568",
language = "English",
volume = "136",
journal = "Journal of cell science",
issn = "1477-9137",
publisher = "The Company of Biologists",
number = "3",
}