Impairment of RPN4, a transcription factor, induces ER stress and lipid abnormality in Saccharomyces cerevisiae.

Abstract

Accumulation of misfolded/unfolded proteins in the endoplasmic reticulum (ER) induces ER stress. The transcription factor RPN4 {"Regulatory Particle Non-ATPase"} regulates protein homeostasis by degrading proteins that elude proper folding or assembly via the proteasomal degradation pathway. Here, we studied the lipid alterations exerted by Saccharomyces cerevisiae to mitigate (ER) stress during adaptive responses in rpn4∆ cells. The loss of RPN4-induced ER stress increased phospholipid synthesis, leading to altered membrane structures and accumulation of neutral lipids, causing an increase in lipid droplets (LDs). There was a significant upregulation of genes involved in neutral lipid and membrane lipid synthesis in rpn4∆ cells. Overexpression of RPN4 restored the defects caused by rpn4∆ cells. Thus, our study provides new insight that RPN4 impacts lipid homeostasis.