Phosphoproteomic Analysis across the Yeast Life Cycle Reveals Control of Fatty Acyl Chain Length by Phosphorylation of the Fatty Acid Synthase Complex

Cell Reports

Berwyck L.J. Poad¹  David L. Marshall¹  Stephen J. Blanksby¹  Martin Hermansson²  Fernando Martínez-Montañés²  Christer S. Ejsing²  Marta Moreno-Torres²  Albert Casanovas²  Ole N. Jensen²  Richard R. Sprenger²  Magdalena Topolska² 

[1] Central Analytical Research Facility, Institute for Future Environments, Queensland University of Technology, Brisbane, QLD 4000, Australia;Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark;

关键词: Saccharomyces cerevisiae;    phosphoproteomics;    signaling pathways;    lipid metabolism;    lipidomics;    flux analysis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: The ability to remodel lipid metabolism under changing conditions is pivotal for cellular functionality and homeostasis. Here, we characterize the regulatory landscape of phosphorylation-based signaling events across the life cycle of Saccharomyces cerevisiae and determine its impact on the regulation of lipid metabolism. Our data show that 50 lipid metabolic proteins are differentially phosphorylated as cells transit between different physiological states. To identify functional phosphosites, we devised a strategy where multiple phosphosites are simultaneously mutated into phosphomimetic or phosphodeficient alleles and mutants are phenotyped by in-depth lipidomics flux analysis. This uncovers functional phosphosites in the phosphatidate cytidylyltransferase Cds1, the phosphatidylserine synthase Cho1, and Fas2, the α-subunit of the fatty acid synthase (FAS) complex. Furthermore, we show that the fatty acyl chain length produced by FAS is governed by phosphorylation. Overall, our work demonstrates a vital role for phosphoregulation of lipid metabolism and provides a resource to investigate its molecular underpinnings.

【 授权许可】

Unknown