Phospholipid homeostasis in biological membranes is essential to maintain functions of organelles such as the endoplasmic reticulum. Phospholipid perturbation has been associated to cellular stress responses. However, in most cases, the implication of membrane lipid changes to homeostatic cellular response has not been clearly defined. Previously, we reported that Saccharomyces cerevisiae adapts to lipid bilayer stress by upregulating several protein quality control pathways such as the endoplasmic reticulum-associated degradation (ERAD) pathway and the unfolded protein response (UPR). Surprisingly, we observed certain ER-resident transmembrane proteins, which form part of the UPR programme, to be destabilised under lipid bilayer stress. Among these, the protein translocon subunit SBH1 was prematurely degraded by membrane stiffening at the ER. Moreover, our findings suggest that the Doa10 complex recognises free SBH1 that becomes increasingly accessible during lipid bilayer stress, perhaps due to the change in ER membrane properties. Premature removal of key ER-resident transmembrane proteins might be an underlying cause of chronic ER stress as a result of lipid bilayer stress.

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Journal Article | Research Support, Non-U.S. Gov't

Authors

Shyu P, Ng BSH, Ho N, Chaw R, Seah YL, Marvalim C, Thibault G

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