{"doi":"10.1101/gad.352979.125","title":"Longevity-promoting mitochondrial unfolded protein response activation requires elements of the PeBoW complex","abstract":"Mitochondria play a crucial role in cellular energy metabolism and homeostasis and are strongly implicated in aging and age-related diseases. The outer mitochondrial membrane protein voltage-dependent anion channel (VDAC) plays multiple roles in mitochondrial homeostasis, including transport of metabolites, ATP, and Ca 2+ . Dysregulation of VDAC levels has been associated with cancer, neurodegeneration, metabolic disorders, and aging. Previously, we demonstrated that elevated VDAC-1 levels in Caenorhabditis elegans lead to increased mitochondrial permeability and reduced life span. Here we demonstrate that reduced VDAC-1 function extends life span through the activation of the mitochondrial unfolded protein response (UPR mt ), a conserved stress response that maintains mitochondrial proteostasis and is linked to life span extension in multiple species. Leveraging unbiased genomic discovery, we identified genes encoding several proteins in the PeBoW complex as a critical mediator of UPR mt activation following VDAC-1 loss. More broadly, we demonstrated a universal requirement for several PeBoW component genes across diverse mitochondrial stressors in order to fully animate the UPR mt . Our findings reveal a heretofore unappreciated role for PeBoW components in UPR mt induction and life span extension in response to mitochondrial stress, highlighting its essential function in mitochondrial quality control and longevity pathways.","journal":"Genes & Development","year":2025,"id":579454,"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":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1490050,"name":"Niclole Stuhr","orcid":null,"position":1,"is_corresponding":false},{"id":920526,"name":"Yifei Zhou","orcid":"0000-0003-0088-6262","position":2,"is_corresponding":false},{"id":672590,"name":"Yuyao Zhang","orcid":"0000-0002-8442-9693","position":3,"is_corresponding":false},{"id":920523,"name":"Armen Yerevanian","orcid":"0000-0003-4985-1028","position":4,"is_corresponding":false},{"id":299215,"name":"Alexander A. Soukas","orcid":"0000-0002-9100-2436","position":5,"is_corresponding":false},{"id":921142,"name":"Adebanjo Adedoja","orcid":null,"position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:58:30.282164Z","pmid":"41162154","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":[]}