Differential Roles of Longevity Assurance Genes LAG1 and LAC1 in Regulating Endoplasmic Reticulum stress and Lipid Homeostasis in Saccharomyces cerevisiae

Yeast ceramide synthesis is regulated by two homologous genes, LAC1 and LAG1, each with distinct physiological roles, especially under ER stress conditions. This study examines their specific functions in lipid homeostasis and the ER stress response. Deleting LAG1 enhances cell growth and survival under ER stress, whereas LAC1 deletion does not provide similar resistance. In contrast, LAG1 deletion significantly impacts phospholipid and neutral lipid metabolism without altering the expression of key ER stress response genes. In comparison, LAG1 overexpression, unlike LAC1 overexpression, severely impairs cell growth and viability, induces ER stress responses, disrupts phospholipid biosynthesis, alters membrane morphology, modifies neutral lipid synthesis, and reduces lipid droplet numbers. Overall, LAG1 uniquely regulates ER stress and lipid homeostasis, independent of its function in ceramide synthesis. Understanding the specific contributions of LAG1 to lipid homeostasis and ER stress provides valuable insight into cellular stress mechanisms.