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Item Methionine Restriction Impairs Degradation of a Protein that Aberrantly Engages the Endoplasmic Reticulum Translocon(Caltech LIbrary, 2023-11-09) Runnebohm, Avery M.; Indovina, Christopher J.; Turk, Samantha M.; Bailey, Connor G.; Orchard, Cade J.; Wade, Lauren; Overton, Danielle L.; Snow, Brian J.; Rubenstein, Eric M.; Biochemistry and Molecular Biology, School of MedicineProteins that persistently engage endoplasmic reticulum (ER) translocons are degraded by multiple translocon quality control (TQC) mechanisms. In Saccharomyces cerevisiae , the model translocon-associated protein Deg1 -Sec62 is subject to ER-associated degradation (ERAD) by the Hrd1 ubiquitin ligase and, to a lesser extent, proteolysis mediated by the Ste24 protease. In a recent screen, we identified nine methionine-biosynthetic genes as candidate TQC regulators. Here, we found methionine restriction impairs Hrd1-independent Deg1 -Sec62 degradation. Beyond revealing methionine as a novel regulator of TQC, our results urge caution when working with laboratory yeast strains with auxotrophic mutations, often presumed not to influence cellular processes under investigation.