{"doi":"10.3389/fcell.2023.1150158","title":"Editorial: Protein homeostasis in growth, development and disease","abstract":"The transition of a linear polypeptide chain into a functional, 3-dimensional protein is fraught with dangers, but a successful outcome is critical to all aspects of life. To assist and monitor this process, all cells and organism are endowed with a cadre of molecular chaperones, their co-factors and folding enzymes (Balchin, Hayer-Hartl, & Hartl, 2016). The ability of the cell to rapidly regulate the availability of these chaperones and folding enzymes is necessary to maintain cellular and organellar homeostasis in response to changes in secretory capacity or alterations in the cellular environment that adversely affect protein folding (Richter, Haslbeck, & Buchner, 2010), (Walter & Ron, 2011). Imbalances in these can lead to disease. In addition to these ubiquitously expressed components of protein folding and quality control systems, tissuespecific factors exist that are more restrictive in their clients and are often important in developmental and differentiation processes. This issue is comprised of a combination of original research articles and reviews that address cutting edge work in this field.As polypeptide chains emerge from the ribosome, they can begin to fold co-translationally, which could inhibit appropriate interactions with more distal sequences needed to reach their native states. Chaperone families including Hsp70, Hsp90 and the cage-like chaperonins are found in all lineages of organisms (bacteria, archaea, and both plant and animal eukaryotes) and serve to protect reactive regions on nascent proteins. They are particularly non-selective and can recognize a vast number of sequence unrelated proteins and can therefore be considered generalists. Hsp70s recognize linear stretches of amino acids that are hydrophobic in nature and will ultimately be buried upon correct protein folding and/or assembly (Blond-Elguindi et al., 1993). They prevent misfolding by protecting these regions but do not directly contribute to folding. Conversely, the chaperonins are multi-subunit ring structures that provide a protective cavity that accommodates partially folded clients and drives their proper maturation through nucleotide-dependent interactions between the various subunits and the incompletely folded client (Gestaut, Limatola, Joachimiak, & Frydman, 2019). One review in this series addresses recent findings that contribute to our understanding of how the mammalian chaperonin TRiC (Tailless complex polypeptide 1 (TCP-1) Ring Complex) is able to contribute to the folding of proteins too large to fit into its central cavity (Ghozlan, Cox, Nierenberg, King, & Khaled, 2022). Another review focuses on prefoldin, an adapter that conveys clients to TRiC to maintain protein homeostasis in physiological and pathological conditions (Tahmaz, Shahmoradi Ghahe, & Topf, 2021). A third review summarizes studies revealing the role of generalist chaperones in protecting the proteome of the parasite and in renovating the host proteome to its own benefit (Blatch, 2022).The endoplasmic reticulum (ER) is the gateway into the secretory pathway and is responsible for the biosynthesis of 1/3 of the proteins encoded in the mammalian genome, which includes proteins that are secreted, expressed on the cell surface, or that populate all organelles of the secretory pathway (Dancourt & Barlowe, 2010). Stringent quality control programs comprised of molecular chaperones and folding enzymes aid and monitor the maturation of nascent proteins entering this organelle (Wiseman, Mesgarzadeh, & Hendershot, 2022). While bound to the chaperone, incompletely folded clients are prevented from moving further along the secretory pathway due to retention sequences on the chaperones. In the case of most soluble chaperones, the tetrapeptide sequence, KDEL, is encoded at their C-terminus. Should the chaperone exit the ER incorrectly it encounters a KDEL receptor in the intermediate compartment or cis Golgi, which returns it and any bound client to the ER (Lewis, Sweet,","journal":"Frontiers in Cell and Developmental Biology","year":2023,"id":402888,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"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":1180454,"name":"Francesco Fazi","orcid":"0000-0003-2910-7912","position":1,"is_corresponding":false},{"id":701123,"name":"Linda M. Hendershot","orcid":"0000-0002-5473-0274","position":2,"is_corresponding":false},{"id":1180453,"name":"Silvia Masciarelli","orcid":"0000-0002-6738-6281","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T01:20:32.588152Z","pmid":"36814602","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":[]}