Lipid saturation induces degradation of squalene epoxidase for sterol homeostasis and cell survival.

ABSTRACT: A fluid membrane containing a mix of unsaturated and saturated lipids is essential for life. However, it is unclear how lipid saturation might affect lipid homeostasis, membrane-associated proteins, and membrane organelles. Here, we generate temperature-sensitive mutants of the sole fatty acid desaturase gene OLE1 in the budding yeast Saccharomyces cerevisiae Using these mutants, we show that lipid saturation triggers the endoplasmic reticulum-associated degradation (ERAD) of squalene epoxidase Erg1, a rate-limiting enzyme in sterol biosynthesis, via the E3 ligase Doa10-Ubc7 complex. We identify the P469L mutation that abolishes the lipid saturation-induced ERAD of Erg1. Overexpressed WT or stable Erg1 mutants all mislocalize into foci in the ole1 mutant, whereas the s

SUBMITTER: Huang LJ 

PROVIDER: S-EPMC9652772 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature