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NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in Saccharomyces cerevisiae
Actively proliferating cells constantly monitor and readjust their metabolic pathways to ensure the replenishment of phospholipids necessary for membrane biogenesis and intracellular trafficking. In Saccharomyces cerevisiae, multiple studies have suggested that the lysine acetyltransferase complex N...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473759/ https://www.ncbi.nlm.nih.gov/pubmed/28455416 http://dx.doi.org/10.1534/g3.117.041053 |
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author | Dacquay, Louis Flint, Annika Butcher, James Salem, Danny Kennedy, Michael Kaern, Mads Stintzi, Alain Baetz, Kristin |
author_facet | Dacquay, Louis Flint, Annika Butcher, James Salem, Danny Kennedy, Michael Kaern, Mads Stintzi, Alain Baetz, Kristin |
author_sort | Dacquay, Louis |
collection | PubMed |
description | Actively proliferating cells constantly monitor and readjust their metabolic pathways to ensure the replenishment of phospholipids necessary for membrane biogenesis and intracellular trafficking. In Saccharomyces cerevisiae, multiple studies have suggested that the lysine acetyltransferase complex NuA4 plays a role in phospholipid homeostasis. For one, NuA4 mutants induce the expression of the inositol-3-phosphate synthase gene, INO1, which leads to excessive accumulation of inositol, a key metabolite used for phospholipid biosynthesis. Additionally, NuA4 mutants also display negative genetic interactions with sec14-1(ts), a mutant of a lipid-binding gene responsible for phospholipid remodeling of the Golgi. Here, using a combination of genetics and transcriptional profiling, we explore the connections between NuA4, inositol, and Sec14. Surprisingly, we found that NuA4 mutants did not suppress but rather exacerbated the growth defects of sec14-1(ts) under inositol-depleted conditions. Transcriptome studies reveal that while loss of the NuA4 subunit EAF1 in sec14-1(ts) does derepress INO1 expression, it does not derepress all inositol/choline-responsive phospholipid genes, suggesting that the impact of Eaf1 on phospholipid homeostasis extends beyond inositol biosynthesis. In fact, we find that NuA4 mutants have impaired lipid droplet levels and through genetic and chemical approaches, we determine that the genetic interaction between sec14-1(ts) and NuA4 mutants potentially reflects a role for NuA4 in fatty acid biosynthesis. Altogether, our work identifies a new role for NuA4 in phospholipid homeostasis. |
format | Online Article Text |
id | pubmed-5473759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-54737592017-06-27 NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in Saccharomyces cerevisiae Dacquay, Louis Flint, Annika Butcher, James Salem, Danny Kennedy, Michael Kaern, Mads Stintzi, Alain Baetz, Kristin G3 (Bethesda) Investigations Actively proliferating cells constantly monitor and readjust their metabolic pathways to ensure the replenishment of phospholipids necessary for membrane biogenesis and intracellular trafficking. In Saccharomyces cerevisiae, multiple studies have suggested that the lysine acetyltransferase complex NuA4 plays a role in phospholipid homeostasis. For one, NuA4 mutants induce the expression of the inositol-3-phosphate synthase gene, INO1, which leads to excessive accumulation of inositol, a key metabolite used for phospholipid biosynthesis. Additionally, NuA4 mutants also display negative genetic interactions with sec14-1(ts), a mutant of a lipid-binding gene responsible for phospholipid remodeling of the Golgi. Here, using a combination of genetics and transcriptional profiling, we explore the connections between NuA4, inositol, and Sec14. Surprisingly, we found that NuA4 mutants did not suppress but rather exacerbated the growth defects of sec14-1(ts) under inositol-depleted conditions. Transcriptome studies reveal that while loss of the NuA4 subunit EAF1 in sec14-1(ts) does derepress INO1 expression, it does not derepress all inositol/choline-responsive phospholipid genes, suggesting that the impact of Eaf1 on phospholipid homeostasis extends beyond inositol biosynthesis. In fact, we find that NuA4 mutants have impaired lipid droplet levels and through genetic and chemical approaches, we determine that the genetic interaction between sec14-1(ts) and NuA4 mutants potentially reflects a role for NuA4 in fatty acid biosynthesis. Altogether, our work identifies a new role for NuA4 in phospholipid homeostasis. Genetics Society of America 2017-04-28 /pmc/articles/PMC5473759/ /pubmed/28455416 http://dx.doi.org/10.1534/g3.117.041053 Text en Copyright © 2017 Dacquay et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigations Dacquay, Louis Flint, Annika Butcher, James Salem, Danny Kennedy, Michael Kaern, Mads Stintzi, Alain Baetz, Kristin NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in Saccharomyces cerevisiae |
title | NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in Saccharomyces cerevisiae |
title_full | NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in Saccharomyces cerevisiae |
title_fullStr | NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in Saccharomyces cerevisiae |
title_full_unstemmed | NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in Saccharomyces cerevisiae |
title_short | NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in Saccharomyces cerevisiae |
title_sort | nua4 lysine acetyltransferase complex contributes to phospholipid homeostasis in saccharomyces cerevisiae |
topic | Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473759/ https://www.ncbi.nlm.nih.gov/pubmed/28455416 http://dx.doi.org/10.1534/g3.117.041053 |
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