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SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR

The ability to store nutrients in lipid droplets (LDs) is an ancient function that provides the primary source of metabolic energy during periods of nutrient insufficiency and between meals. The Fat storage-Inducing Transmembrane (FIT) proteins are conserved ER–resident proteins that facilitate fat...

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Autores principales: Moir, Robyn D., Gross, David A., Silver, David L., Willis, Ian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426550/
https://www.ncbi.nlm.nih.gov/pubmed/22927826
http://dx.doi.org/10.1371/journal.pgen.1002890
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author Moir, Robyn D.
Gross, David A.
Silver, David L.
Willis, Ian M.
author_facet Moir, Robyn D.
Gross, David A.
Silver, David L.
Willis, Ian M.
author_sort Moir, Robyn D.
collection PubMed
description The ability to store nutrients in lipid droplets (LDs) is an ancient function that provides the primary source of metabolic energy during periods of nutrient insufficiency and between meals. The Fat storage-Inducing Transmembrane (FIT) proteins are conserved ER–resident proteins that facilitate fat storage by partitioning energy-rich triglycerides into LDs. FIT2, the ancient ortholog of the FIT gene family first identified in mammals has two homologs in Saccharomyces cerevisiae (SCS3 and YFT2) and other fungi of the Saccharomycotina lineage. Despite the coevolution of these genes for more than 170 million years and their divergence from higher eukaryotes, SCS3, YFT2, and the human FIT2 gene retain some common functions: expression of the yeast genes in a human embryonic kidney cell line promotes LD formation, and expression of human FIT2 in yeast rescues the inositol auxotrophy and chemical and genetic phenotypes of strains lacking SCS3. To better understand the function of SCS3 and YFT2, we investigated the chemical sensitivities of strains deleted for either or both genes and identified synthetic genetic interactions against the viable yeast gene-deletion collection. We show that SCS3 and YFT2 have shared and unique functions that connect major biosynthetic processes critical for cell growth. These include lipid metabolism, vesicular trafficking, transcription of phospholipid biosynthetic genes, and protein synthesis. The genetic data indicate that optimal strain fitness requires a balance between phospholipid synthesis and protein synthesis and that deletion of SCS3 and YFT2 impacts a regulatory mechanism that coordinates these processes. Part of this mechanism involves a role for SCS3 in communicating changes in the ER (e.g. due to low inositol) to Opi1-regulated transcription of phospholipid biosynthetic genes. We conclude that SCS3 and YFT2 are required for normal ER membrane biosynthesis in response to perturbations in lipid metabolism and ER stress.
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spelling pubmed-34265502012-08-27 SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR Moir, Robyn D. Gross, David A. Silver, David L. Willis, Ian M. PLoS Genet Research Article The ability to store nutrients in lipid droplets (LDs) is an ancient function that provides the primary source of metabolic energy during periods of nutrient insufficiency and between meals. The Fat storage-Inducing Transmembrane (FIT) proteins are conserved ER–resident proteins that facilitate fat storage by partitioning energy-rich triglycerides into LDs. FIT2, the ancient ortholog of the FIT gene family first identified in mammals has two homologs in Saccharomyces cerevisiae (SCS3 and YFT2) and other fungi of the Saccharomycotina lineage. Despite the coevolution of these genes for more than 170 million years and their divergence from higher eukaryotes, SCS3, YFT2, and the human FIT2 gene retain some common functions: expression of the yeast genes in a human embryonic kidney cell line promotes LD formation, and expression of human FIT2 in yeast rescues the inositol auxotrophy and chemical and genetic phenotypes of strains lacking SCS3. To better understand the function of SCS3 and YFT2, we investigated the chemical sensitivities of strains deleted for either or both genes and identified synthetic genetic interactions against the viable yeast gene-deletion collection. We show that SCS3 and YFT2 have shared and unique functions that connect major biosynthetic processes critical for cell growth. These include lipid metabolism, vesicular trafficking, transcription of phospholipid biosynthetic genes, and protein synthesis. The genetic data indicate that optimal strain fitness requires a balance between phospholipid synthesis and protein synthesis and that deletion of SCS3 and YFT2 impacts a regulatory mechanism that coordinates these processes. Part of this mechanism involves a role for SCS3 in communicating changes in the ER (e.g. due to low inositol) to Opi1-regulated transcription of phospholipid biosynthetic genes. We conclude that SCS3 and YFT2 are required for normal ER membrane biosynthesis in response to perturbations in lipid metabolism and ER stress. Public Library of Science 2012-08-23 /pmc/articles/PMC3426550/ /pubmed/22927826 http://dx.doi.org/10.1371/journal.pgen.1002890 Text en © 2012 Moir et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Moir, Robyn D.
Gross, David A.
Silver, David L.
Willis, Ian M.
SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR
title SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR
title_full SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR
title_fullStr SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR
title_full_unstemmed SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR
title_short SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR
title_sort scs3 and yft2 link transcription of phospholipid biosynthetic genes to er stress and the upr
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426550/
https://www.ncbi.nlm.nih.gov/pubmed/22927826
http://dx.doi.org/10.1371/journal.pgen.1002890
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