TY - JOUR T1 - Derlin Dfm1 Employs a Chaperone Function to Resolve Misfolded Membrane Protein Stress JF - bioRxiv DO - 10.1101/2022.01.25.477788 SP - 2022.01.25.477788 AU - Rachel Kandel AU - Jasmine Jung AU - Della Syau AU - Tiffany Kuo AU - Livia Songster AU - Analine Aguayo AU - Sascha Duttke AU - Christopher Benner AU - Sonya Neal Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/01/26/2022.01.25.477788.abstract N2 - Accumulation of misfolded proteins is a known source of cellular stress and can be detrimental to cellular health. While protein aggregation is a known hallmark of many diseases, the mechanisms by which protein aggregates cause toxicity and the molecular machines that prevent this toxicity are not completely understood. Here, we show that the accumulated misfolded membrane proteins form endoplasmic reticulum (ER) localized aggregates, impacting ubiquitin and proteasome homeostasis. Additionally, we have identified a chaperone ability of the yeast rhomboid pseudoprotease Dfm1 to influence solubilization of misfolded membrane proteins and prevent toxicity from misfolded membrane proteins. We establish that this function of Dfm1 does not require recruitment of the ATPase Cdc48 and it is distinct from Dfm1’s previously identified function in dislocating misfolded membrane proteins to the cytosol for degradation.Competing Interest StatementThe authors have declared no competing interest. ER -