{"doi":"10.3389/fcell.2023.1196430","title":"Editorial: The role of mortalin in biology and disease","abstract":"The role of mortalin in biology and diseaseThe heat shock protein (HSP) 70 family chaperones are central regulators of many cellular processes requiring protein quality control.Mortalin (also called mtHSP70, GRP75, PBP74, and HSPA9) is a member of this family initially identified as the mitochondrial HSP70 (Craig et al., 1989;Leustek et al., 1989).While the critical roles of mortalin in different mitochondrial processes are well established, growing evidence suggests that mortalin also has previously unexpected roles outside mitochondria.In line with this, disease-associated mortalin alterations and their pathophysiological significance have been noted.This Research Topic aimed to update recent advances in mortalin functions in different pathophysiological contexts and the potential therapeutic molecules that target mortalin and its protein network.Increasing evidence suggests the significance of mortalin in cancer as its correlation with patient outcomes are often detected in different tumors.Esfahanian et al. review the literature to cover this information and also analyze the RNAseq datasets from the Cancer Genome Atlas (TCGA) database to demonstrate this correlation in different cancers.Esfahanian et al. show that the prognostic impact of mortalin, determined by its RNA levels, can differ between tumors and discuss the factors limiting RNA expression data interpretation.Upregulated mortalin expression confers a survival advantage to different types of tumor cells, rationalizing its candidacy as a therapeutic target.Yoon et al. and Elwakeel introduce a brief history of mortalin beginning from its identification as an antisenescence factor in cells (Wadhwa et al., 1993), which granted the name \"mortalin,\" and review the identification of the tumor suppressor TP53 as a key mortalin interaction partner.Notably, while nuclear localization of TP53 is essential for its tumor-suppressive effects, mortalin can inhibit TP53 nuclear localization by sequestering the tumor suppressor in the cytoplasm.This is a widely known mechanism underlying the pro-tumorigenic effects of mortalin.Elwakeel comprehensively reviews the mortalin-TP53 interaction and the rationale for targeting this physical interaction for tumor suppression.Mortalin functions require various interaction partners, such as co-chaperones, regulators, and clients in different subcellular compartments.Esfahanian et al. review these effectors and regulators of mortalin for mitochondrial and ER homeostasis, trafficking of macromolecules, proteostasis, signal transduction, and complement activation.Esfahanian et al. also review how posttranslational modifications such as phosphorylation, acetylation, oxidation, and ubiquitination affect mortalin function and interactions with its binding partners with a significant focus on UBXN2A-mediated mortalin ubiquitination and degradation.","journal":"Frontiers in Cell and Developmental Biology","year":2023,"id":399013,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":471444,"name":"Jong‐In Park","orcid":"0000-0001-7248-4735","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-19T01:19:51.724387Z","pmid":"37113770","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":[]}