{"doi":"10.1016/j.celrep.2025.115282","title":"Selective clearance of aberrant membrane proteins by TORC1-mediated micro-ER-phagy","abstract":"Aberrant accumulation and clearance of membrane proteins is associated with disease. Membrane proteins are inserted first to the endoplasmic reticulum (ER). During normal growth, two quality control (QC) processes, ER-associated degradation and macro-ER-phagy, deliver misfolded and excess membrane proteins for degradation in the proteasome and lysosome, respectively. We show that in yeast during normal growth, ER-QC is constitutive, since none of the stress-induced signaling pathways-nutritional, proteotoxic, or heat-are involved. In mutant cells defective in ER-QC, misfolded or excess proteins accumulate and nutritional stress, but not proteotoxic or heat stress, can stimulate their clearance. Early during nutritional stress, clearance occurs in the lysosome through a selective micro-ER-phagy pathway dependent on the ubiquitin ligase Rsp5, its Ssh4 adaptor, and ESCRT. In contrast, only a fraction of normal membrane proteins is degraded much later via macro-autophagy. Because the pathways explored here are conserved, nutritional stress emerges as a possible way for clearing disease-associated membrane proteins.","journal":"Cell Reports","year":2025,"id":531082,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1411404,"name":"Yaneris M. Alvarado Cartagena","orcid":null,"position":1,"is_corresponding":false},{"id":912473,"name":"Rakhilya Murtazina","orcid":"0000-0002-0819-9953","position":2,"is_corresponding":false},{"id":1047961,"name":"Sarah F. Zhao","orcid":null,"position":3,"is_corresponding":false},{"id":1411405,"name":"Candela Ximenez de Olaso","orcid":null,"position":4,"is_corresponding":false},{"id":1047287,"name":"Nava Segev","orcid":"0000-0001-9319-0613","position":5,"is_corresponding":false},{"id":1047286,"name":"Valeriya Gyurkovska","orcid":"0000-0001-6564-0066","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"39946230","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}