{"doi":"10.1101/2024.02.22.581543","title":"Non-cell-autonomous regulation of germline proteostasis by insulin/IGF-1 signaling via the intestinal peptide transporter PEPT-1","abstract":"Abstract Gametogenesis involves active protein synthesis and heavily relies on proteostasis. How animals regulate germline proteostasis at the organismal level is poorly understood. Taking C. elegans as a model, we show that germline proteostasis requires coupled activities of HSF-1-dependent protein folding and insulin/IGF-1 signaling controlled protein synthesis. Depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, declines in fecundity and gamete quality. Reduced insulin/IGF-1 signaling confers germ cells’ resilience to limited protein folding capacity and proteotoxic stress by lowering ribosome biogenesis and the rate of translation. Interestingly, insulin/IGF-1 signaling promotes the expression of the evolutionarily conserved intestinal peptide transporter PEPT-1 via its downstream transcription factor FOXO/DAF-16, therefore allowing dietary proteins to be incorporated into an amino acid pool that fuels protein synthesis in the germline. We propose that this non-cell-autonomous pathway plays a critical role in regulating proteostasis in gametogenesis. Teaser Insulin/IGF-1 signaling regulates proteostasis in gametogenesis via the control of dietary protein absorption.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490113,"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":0.9582,"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":334922,"name":"Stacey L. Edwards","orcid":"0000-0001-7428-4139","position":1,"is_corresponding":false},{"id":696676,"name":"Allison C. Morphis","orcid":"0000-0002-9849-4402","position":2,"is_corresponding":false},{"id":1298560,"name":"Mary V. Johnson","orcid":null,"position":3,"is_corresponding":false},{"id":1335356,"name":"Vitor Oliveira","orcid":"0000-0002-4662-1377","position":4,"is_corresponding":false},{"id":696678,"name":"Tomasz Chamera","orcid":"0000-0003-2646-0550","position":5,"is_corresponding":false},{"id":956671,"name":"Siyan Liu","orcid":"0000-0001-8452-6349","position":6,"is_corresponding":false},{"id":1298154,"name":"Nhat Dang Huy Nguyen","orcid":"0000-0002-1107-7033","position":7,"is_corresponding":false},{"id":439336,"name":"Jian Li","orcid":"0000-0001-5168-6610","position":8,"is_corresponding":false},{"id":1120791,"name":"Tahir Muhammad","orcid":"0000-0001-8652-2042","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:08:32.775003Z","pmid":null,"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":[]}