The Role of lysine Acetylation on the Regulation of Phospholipid Homeostasis in Yeast

Title: The Role of lysine Acetylation on the Regulation of Phospholipid Homeostasis in Yeast
Authors: Dacquay, Louis
Date: 2017
Embargo: 2019-03-02
Abstract: Actively proliferating cells constantly monitor and re-adjust their metabolic pathways to ensure the replenishment of phospholipids necessary for membrane biogenesis and intracellular trafficking. In Saccharomyces cerevisiae, multiple studies have suggested that lysine acetylation has a role in coordinating phospholipid metabolism, yet its contribution towards phospholipid homeostasis remains uncharacterized. In this study we undertook a genetic screen to explore the connection between lysine acetylation and phospholipid homeostasis. We found that mutants of the lysine acetyltransferase complex, NuA4, shared a negative genetic interaction with a mutant of Sec14, a lipid-binding protein that regulates Golgi phospholipid composition. Through transcriptome, genetic, cell biology, and chemical analysis, we discovered that the growth defects between NuA4 and Sec14 mutants is likely derived from impaired fatty acid biosynthesis suggesting a role for NuA4 as a positive regulator of fatty acid biosynthesis. Secondly, we discovered that acetylation on the conserved lysine residue K109 inhibits the localization and function of the Oxysterol-Binding Protein Osh4- a lipid-binding protein that antagonizes the function of Sec14 at the Golgi. Furthermore, regulation of Oxysterol-Binding Proteins by acetylation may be a conserved mechanism as we found that Osh1, a homologue of Osh4, was also acetylated on the equivalent lysine residue. Altogether, we have demonstrated that lysine acetylation can target multiple different phospholipid metabolic pathways which implies that it has a very important role for the regulation of phospholipid homeostasis.
CollectionThèses - Embargo // Theses - Embargo