Runnebohm, Avery M.Indovina, Christopher J.Turk, Samantha M.Bailey, Connor G.Orchard, Cade J.Wade, LaurenOverton, Danielle L.Snow, Brian J.Rubenstein, Eric M.2024-04-172024-04-172023-11-09Runnebohm AM, Indovina CJ, Turk SM, et al. Methionine Restriction Impairs Degradation of a Protein that Aberrantly Engages the Endoplasmic Reticulum Translocon. MicroPubl Biol. 2023;2023:10.17912/micropub.biology.001021. Published 2023 Nov 9. doi:10.17912/micropub.biology.001021https://hdl.handle.net/1805/40092Proteins 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.en-USAttribution 4.0 InternationalEndoplasmic reticulum (ER) transloconsSaccharomyces cerevisiaeMethionineArticle