Systematic lipidomic analysis of yeast protein kinase and phosphatase mutants reveals novel insights into regulation of lipid homeostasis.
Bottom Line: 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.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.
Affiliation: Department of Biochemistry, University of Geneva, Geneva CH-1211, Switzerland National Centre of Competence in Research "Chemical Biology,", University of Geneva, Geneva CH-1211, Switzerland.Show MeSH
Mentions: As a first unbiased attempt to find the similarities between lipid profiles of different mutants, we generated a correlation matrix of the mutants (Figure 2A). Two prominent clusters emerged, enriched in components of amino acid– and glucose-sensing pathways. By this exploratory approach, when one plots the quantities of all lipids relative to wild type for the 127 strains, high complexity is seen (Supplemental Figure S3A), suggesting that diverse signaling pathways control different aspects of lipid homeostasis. Of importance, using an unbiased clustering analysis, the vps15 and vps34 mutants clustered adjacent to each other. The two corresponding proteins are members of the same functional complex involved in autophagy and protein sorting (Obara et al., 2008). This shows that our method of lipid profiling can give valuable information about biological function. This has important consequences because it suggests that determination of lipid profile is a useful tool to identify potential defects in cellular signaling pathways. Lipid alterations associated with disease could therefore be useful biomarkers to pinpoint disease mechanisms.
Affiliation: Department of Biochemistry, University of Geneva, Geneva CH-1211, Switzerland National Centre of Competence in Research "Chemical Biology,", University of Geneva, Geneva CH-1211, Switzerland.