Analysis on the mechanism of ER membrane proliferation upon ER protein overproduction in yeast

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Endoplasmic reticulum (ER) is the center of secretory protein and lipid syntheses in eukaryotic cells. Although it has been attracted many researchers who are interested in those biosynthetic pathways, its proliferation and biogenesis are not yet well understood. We overproduced an ER membrane protein cytochrome P450Alk1 of Candida maltosa in Saccharomyces cerevisiae and analyzed the mechanism of the resultant ER proliferation, especially in the aspects of ER chaperone induction and membrane lipid metabolism. The results are; 1) There is no enhanced synthesis of membrane phospholipids during ER proliferation. 2) The requirement of Ire1p for ER proliferation is dependent on the genetic backgrounds of employed yeast strains. 3) Degradation of ER misfolded proteins does not necessarily occur by the proteasome system. 4) We established a system where yeast growth is dependent on the externally-supplied phospholipids. This enables us to analyze membrane lipid metabolism during ER protein-induced ER proliferation.