Wang, B.B.Apaja, P.M.2025-07-212025-07-212022Autophagy Reports, 2022; 1(1):260-2632769-41272769-4127https://hdl.handle.net/2440/146197Protein quality control (PQC) is a conformational surveillance system critical to maintaining native protein composition in the cell. However, PQC mechanisms at the endo-lysosomal pathway especially toward membrane proteins and during cumulative endo-lysosomal stress are incompletely understood. We recently identified the ubiquitin ligase UBR1 as a PQC E3 ubiquitin-ligase for endosomal and/or cytosolic Ca²⁺-increase mediated proteostasis disease stress. As a consequence of the endosomal stress and/or cytosolic Ca²⁺-increase, the QC pathway using selective endosomal autophagy (endophagy) and autophagy was activated for ubiquitinated and arginylated UBR1-SQSTM1/p62 cargoes. In turn, the loss of UBR1, arginylation or both evoke endo-lysosomal pathway stress. Our data suggest that UBR1 with arginylation-dependent endophagy and autophagy is required during proteostasis perturbations and highlight the importance of UBR1 in stressinduced autophagy QC with implications for various human diseases.en© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.autophagosome; endosome; lysosome; proteostasis stress; regeneration; SQSTM1/p62; ubiquitinationJournal article10.1080/27694127.2022.2097274616870Apaja, P.M. [0000-0002-1622-2332]