Null Mutation in IRE1 Gene Inhibits Overproduction of Microsomal Cytochrome P450Alkl (CYP 52A3) and Proliferation of the Endoplasmic Reticulum in Saccharomyces cerevisiae

Abstract

Overproduction of microsomal cytochrome P450Alkl (P450Alkl) of Candida maltosa in Saccharomyces cerevisiae resulted in an extensive proliferation of endoplasmic reticulum (ER) and induction of Kar2p and Pdilp. The irel null mutation severely suppressed ER proliferation, reduced the level of functional P450Alkl, and showed no induction of these ER chaperones, suggesting that the function of Irelp is required for ER proliferation upon the overproduction of P450Alkl. Cerulenin, a potent inhibitor of lipid biosynthesis, also induced these chaperones in an Irelp-dependent manner and limited the production of functional P450Alkl. These results imply that Irelp may function to restore the balance between membrane proteins and lipids of the ER when the ER is relatively overcrowded by membrane proteins.