{"doi":"10.1111/jnc.16043","title":"Arrestin‐3 binds parkin and enhances parkin‐dependent mitophagy","abstract":"Arrestins were discovered for their role in homologous desensitization of G-protein-coupled receptors (GPCRs). Later non-visual arrestins were shown to regulate several signaling pathways. Some of these pathways require arrestin binding to GPCRs, the regulation of others is receptor independent. Here, we demonstrate that arrestin-3 binds the E3 ubiquitin ligase parkin via multiple sites, preferentially interacting with its RING0 domain. Identification of the parkin domains involved suggests that arrestin-3 likely relieves parkin autoinhibition and/or stabilizes the enzymatically active \"open\" conformation of parkin. Arrestin-3 binding enhances ubiquitination by parkin of the mitochondrial protein mitofusin-1 and facilitates parkin-mediated mitophagy in HeLa cells. Furthermore, arrestin-3 and its mutant with enhanced parkin binding rescue mitofusin-1 ubiquitination and mitophagy in the presence of the Parkinson's disease-associated R275W parkin mutant, which is defective in both functions. Thus, modulation of parkin activity via arrestin-3 might be a novel strategy of anti-parkinsonian therapy.","journal":"Journal of Neurochemistry","year":2024,"id":437612,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9452,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":141878,"name":"Kevin Nguyen","orcid":null,"position":1,"is_corresponding":false},{"id":382923,"name":"Sergey A. Vishnivetskiy","orcid":"0000-0001-8619-4157","position":2,"is_corresponding":false},{"id":271822,"name":"Vsevolod V. Gurevich","orcid":"0000-0002-3950-5351","position":3,"is_corresponding":false},{"id":271823,"name":"Eugenia V. Gurevich","orcid":"0000-0002-0563-8295","position":4,"is_corresponding":false},{"id":395410,"name":"Chen Zheng","orcid":"0000-0002-3610-5715","position":0,"is_corresponding":true}],"reference_count":111,"raw_metadata":null,"created_at":"2026-07-19T02:00:34.490087Z","pmid":"38196269","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":[]}