{"doi":"10.1101/2022.12.15.520639","title":"Cell non-autonomous control of autophagy and metabolism by glial cells","abstract":"SUMMARY Glia are the protectors of the nervous system, providing neurons with support and protection from cytotoxic insults. We previously discovered that four astrocyte-like glia can regulate organismal proteostasis and longevity in C. elegans . Expression of the UPR ER transcription factor, XBP-1s, in these glia increases stress resistance, longevity, and activates the UPR ER in intestinal cells via neuropeptides. Autophagy, a key regulator of metabolism and aging, has been described as a cell autonomous process. Surprisingly, we find that glial XBP-1s enhances proteostasis and longevity by cell non-autonomously reprogramming organismal lipid metabolism and activating autophagy. Glial XBP-1s regulates the activation of another transcription factor, HLH-30/TFEB, in the intestine. HLH-30 activates intestinal autophagy, increases intestinal lipid catabolism, and upregulates a robust transcriptional program. Our study reveals a novel role for glia in regulating peripheral lipid metabolism, autophagy, and organellar health through peripheral activation of HLH-30 and autophagy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":305057,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":258500,"name":"Samira Monshietehadi","orcid":"0000-0002-2910-7739","position":1,"is_corresponding":false},{"id":329549,"name":"Arushi Sahay","orcid":"0000-0002-8284-8034","position":2,"is_corresponding":false},{"id":258493,"name":"Ashley E. Frakes","orcid":"0000-0001-8424-0770","position":3,"is_corresponding":false},{"id":258497,"name":"Jenni Durieux","orcid":"0000-0002-0016-7332","position":4,"is_corresponding":false},{"id":998516,"name":"Martina Velichkovska","orcid":"0000-0003-1991-4163","position":5,"is_corresponding":false},{"id":998979,"name":"Cesar Mena","orcid":null,"position":6,"is_corresponding":false},{"id":998517,"name":"Amelia Farinas","orcid":"0000-0002-6697-8883","position":7,"is_corresponding":false},{"id":340283,"name":"Melissa Sanchez","orcid":"0000-0002-4403-3977","position":8,"is_corresponding":false},{"id":258501,"name":"Andrew Dillin","orcid":"0000-0002-7427-2629","position":9,"is_corresponding":false},{"id":258494,"name":"Melissa G. Metcalf","orcid":"0000-0003-0515-5784","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:37.185846Z","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":[]}