Systematic lipidomic analysis of yeast protein kinase and phosphatase mutants reveals novel insights into regulation of lipid homeostasis
| Autor: | Aline X.S. Santos, Fabrice P. A. David, Manuele Piccolis, Isabelle Riezman, Maria Auxiliadora Aguilera-Romero, Olivier Schaad, Robbie Loewith, Howard Riezman |
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| Rok vydání: | 2014 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Saccharomyces cerevisiae Phosphatase Glycerophospholipids Protein Kinases/genetics Phosphoric Monoester Hydrolases/genetics Mass Spectrometry Saccharomyces cerevisiae/genetics chemistry.chemical_compound Lipids/analysis ddc:590 ddc:570 Sphingolipids/analysis/metabolism Transcriptional regulation Homeostasis Protein kinase A Molecular Biology Sterols/analysis/metabolism Sphingolipids biology Kinase Glycerophospholipids/analysis/metabolism Systems Biology Lipid metabolism Cell Biology Articles biology.organism_classification Lipid Metabolism Sphingolipid Lipids Phosphoric Monoester Hydrolases Cell biology Sterols chemistry Biochemistry Glycerophospholipid ddc:540 Mutation Saccharomyces cerevisiae Proteins/genetics lipids (amino acids peptides and proteins) Protein Kinases |
| Zdroj: | Molecular biology of the cell Molecular Biology of the Cell, Vol. 25, No 20 (2014) pp. 3234-3246 Molecular Biology of the Cell |
| ISSN: | 1059-1524 |
| DOI: | 10.1091/mbc.E14-03-0851 |
| Popis: | An unbiased mass spectrometry–based lipidomic screening method is used to analyze the major lipids of yeast deletions in protein kinase/phosphatase genes. This creates a new, rich source of biological insight. It uncovers new players in lipid homeostasis and gives a useful data set to further the understanding of lipid regulation by signaling networks. The regulatory pathways required to maintain eukaryotic lipid homeostasis are largely unknown. We developed a systematic approach to uncover new players in the regulation of lipid homeostasis. Through an unbiased mass spectrometry–based lipidomic screening, we quantified hundreds of lipid species, including glycerophospholipids, sphingolipids, and sterols, from a collection of 129 mutants in protein kinase and phosphatase genes of Saccharomyces cerevisiae. Our approach successfully identified known kinases involved in lipid homeostasis and uncovered new ones. By clustering analysis, we found connections between nutrient-sensing pathways and regulation of glycerophospholipids. Deletion of members of glucose- and nitrogen-sensing pathways showed reciprocal changes in glycerophospholipid acyl chain lengths. We also found several new candidates for the regulation of sphingolipid homeostasis, including a connection between inositol pyrophosphate metabolism and complex sphingolipid homeostasis through transcriptional regulation of AUR1 and SUR1. This robust, systematic lipidomic approach constitutes a rich, new source of biological information and can be used to identify novel gene associations and function. |
| Databáze: | OpenAIRE |
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