Uncovering the Role of the Yeast Lysine Acetyltransferase NuA4 in the Regulation of Nuclear Shape and Lipid Metabolism

• Published in: Molecular and cellular biology 2024-07, Vol.44 (7), p.273-288
• Main Authors: Laframboise, Sarah Jane, Deneault, Lauren F, Denoncourt, Alix, Downey, Michael, Baetz, Kristin
• Format: Article
• Language: English
• Subjects: Acetylation; Cell Biology; Cell Nucleus - metabolism; deformation; diacylglycerols; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Lipid Metabolism; lysine N-acetyltransferase; Mutation; Nuclear Envelope - metabolism; nuclear membrane; Phosphatidate Phosphatase - genetics; Phosphatidate Phosphatase - metabolism; phosphatidic acids; Phospholipids - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; vacuoles; Vacuoles - metabolism; yeasts
• ISSN: 1098-5549; 0270-7306; 1098-5549
• DOI: 10.1080/10985549.2024.2366206

Here, we report a novel role for the yeast lysine acetyltransferase NuA4 in regulating phospholipid availability for organelle morphology. Disruption of the NuA4 complex results in 70% of cells displaying nuclear deformations and nearly 50% of cells exhibiting vacuolar fragmentation. Cells deficient in NuA4 also show severe defects in the formation of nuclear-vacuole junctions (NJV), as well as a decrease in piecemeal microautophagy of the nucleus (PMN). To determine the cause of these defects we focused on Pah1, an enzyme that converts phosphatidic acid into diacylglycerol, favoring accumulation of lipid droplets over phospholipids that are used for membrane expansion. NuA4 subunit Eaf1 was required for Pah1 localization to the inner nuclear membrane and artificially tethering of Pah1 to the nuclear membrane rescued nuclear deformation and vacuole fragmentation defects, but not defects related to the formation of NVJs. Mutation of a NuA4-dependent acetylation site on Pah1 also resulted in aberrant Pah1 localization and defects in nuclear morphology and NVJ. Our work suggests a critical role for NuA4 in organelle morphology that is partially mediated through the regulation of Pah1 subcellular localization.