{"doi":"10.1111/ajt.16882","title":"Modulating donor mitochondrial fusion/fission delivers immunoprotective effects in cardiac transplantation","abstract":"Early insults associated with cardiac transplantation increase the immunogenicity of donor microvascular endothelial cells (ECs), which interact with recipient alloreactive memory T cells and promote responses leading to allograft rejection. Thus, modulating EC immunogenicity could potentially alter T cell responses. Recent studies have shown modulating mitochondrial fusion/fission alters immune cell phenotype. Here, we assess whether modulating mitochondrial fusion/fission reduces EC immunogenicity and alters EC-T cell interactions. By knocking down DRP1, a mitochondrial fission protein, or by using the small molecules M1, a fusion promoter, and Mdivi1, a fission inhibitor, we demonstrate that promoting mitochondrial fusion reduced EC immunogenicity to allogeneic CD8+ T cells, shown by decreased T cell cytotoxic proteins, decreased EC VCAM-1, MHC-I expression, and increased PD-L1 expression. Co-cultured T cells also displayed decreased memory frequencies and Ki-67 proliferative index. For in vivo significance, we used a novel murine brain-dead donor transplant model. Balb/c hearts pretreated with M1/Mdivi1 after brain-death induction were heterotopically transplanted into C57BL/6 recipients. We demonstrate that, in line with our in vitro studies, M1/Mdivi1 pretreatment protected cardiac allografts from injury, decreased infiltrating T cell production of cytotoxic proteins, and prolonged allograft survival. Collectively, our data show promoting mitochondrial fusion in donor ECs mitigates recipient T cell responses and leads to significantly improved cardiac transplant survival.","journal":"American Journal of Transplantation","year":2021,"id":180723,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":476909,"name":"Zhenxiao Tu","orcid":"0009-0005-0350-898X","position":1,"is_corresponding":false},{"id":295603,"name":"Ali Alawieh","orcid":"0000-0003-2601-8850","position":2,"is_corresponding":false},{"id":371308,"name":"Jennifer K. Mulligan","orcid":"0000-0001-6880-6092","position":3,"is_corresponding":false},{"id":730830,"name":"Scott Esckilsen","orcid":null,"position":4,"is_corresponding":false},{"id":725677,"name":"Kristen M. Quinn","orcid":"0000-0002-2373-2074","position":5,"is_corresponding":false},{"id":377096,"name":"Kamala Sundararaj","orcid":"0009-0004-5049-9767","position":6,"is_corresponding":false},{"id":730194,"name":"Caroline Wallace","orcid":"0000-0001-8960-756X","position":7,"is_corresponding":false},{"id":730195,"name":"Ryan Finnegan","orcid":"0000-0002-4979-6906","position":8,"is_corresponding":false},{"id":730831,"name":"Patterson Allen","orcid":null,"position":9,"is_corresponding":false},{"id":242937,"name":"Shikhar Mehrotra","orcid":"0000-0002-5411-9504","position":10,"is_corresponding":false},{"id":314038,"name":"Carl Atkinson","orcid":"0000-0002-0067-0210","position":11,"is_corresponding":false},{"id":661549,"name":"Satish N. Nadig","orcid":"0000-0001-6090-4245","position":12,"is_corresponding":false},{"id":730193,"name":"Danh T. Tran","orcid":"0000-0002-8200-9257","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:47:57.268805Z","pmid":"34714588","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":[]}