{"doi":"10.1101/2024.09.16.613298","title":"Hemoglobin alpha is a redox-sensitive mitochondrial-related protein in T-lymphocytes","abstract":"Hemoglobin subunits, which form the well-characterized, tetrameric, oxygen-carrying protein, have recently been described to be expressed in various non-canonical cell types. However, the exact function of hemoglobin subunits within these cells remains to be fully elucidated. Herein, we report for the first time, the expression of hemoglobin alpha-a1 (Hba-a1) in T-lymphocytes and describe its role as a mitochondrial-associated antioxidant. Within naïve T-lymphocytes, Hba-a1 mRNA and HBA protein are present and highly induced by redox perturbations, particularly those arising from the mitochondria. Additionally, preliminary data using a T-lymphocyte specific Hba-a1 knock-out mouse model indicated that the loss of Hba-a1 led to an exacerbated production of mitochondrial reactive oxygen species and inflammatory cytokines after a stress challenge, further supporting the role of HBA acting to buffer the mitochondrial redox environment. Interestingly, we observed Hba-a1 expression to be significantly upregulated or downregulated depending on T-lymphocyte polarization and metabolic state, which appeared to be controlled by both transcriptional regulation and chromatin remodeling. Altogether, these data suggest Hba-a1 may function as a crucial mitochondrial-associated antioxidant and appears to possess critical and complex functions related to T-lymphocyte activation and differentiation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489022,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"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":1258928,"name":"Valeria A. Silva","orcid":null,"position":1,"is_corresponding":false},{"id":1258929,"name":"Kristen R. Giebel","orcid":null,"position":2,"is_corresponding":false},{"id":1221472,"name":"Tamara Natour","orcid":"0009-0005-1084-464X","position":3,"is_corresponding":false},{"id":923286,"name":"Tatlock H. Lauten","orcid":null,"position":4,"is_corresponding":false},{"id":1233797,"name":"Caroline N Jojo","orcid":null,"position":5,"is_corresponding":false},{"id":1258930,"name":"Abigail E. Schleiker","orcid":null,"position":6,"is_corresponding":false},{"id":314765,"name":"Adam J. Case","orcid":"0000-0003-3404-1428","position":7,"is_corresponding":false},{"id":1258927,"name":"Emily Reed","orcid":null,"position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:08:23.929823Z","pmid":"39345360","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":[]}