Abstract
Membrane organelles are dynamic structures that depend on fluid membranes for their integrity and function, with the fluidity primarily derived from loosely packed unsaturated lipids. We investigated how cells respond to lipid saturation and its effect on nuclear dynamics in the budding yeast Saccharomyces cerevisiae. We found that the lipid desaturase mutant ole1-20 upregulates various genes, including OLE1, primarily through the lipid saturation-sensing transcription factor Mga2. The ole1-20 mutant displays prolonged anaphase and impaired nuclear membrane expansion, which can be rescued by the membrane fluidizer glycerol and by enhanced glycerophospholipid synthesis. However, deleting MGA2 or inhibiting de novo glycerophospholipid synthesis exacerbates mitotic phenotypes in ole1-20, leading to mitotic spindle bending, unequal nuclear division, and transient nuclear leakage. Our study underscores the importance of lipid unsaturation in nuclear dynamics during mitosis and highlights the crucial role of Mga2-mediated gene regulation in maintaining glycerophospholipid homeostasis necessary for proper nuclear membrane expansion and division in response to lipid saturation.