{"doi":"10.1126/sciadv.adp7444","title":"The adenine nucleotide translocase family underlies cardiac ischemia-reperfusion injury through the mitochondrial permeability pore independently of cyclophilin D","abstract":"The mitochondrial permeability transition pore (mPTP) is implicated in cardiac ischemia-reperfusion (I/R) injury. During I/R, elevated mitochondrial Ca 2+ triggers mPTP opening, leading to necrotic cell death. Although nonessential regulators of this pore are characterized, the molecular identity of the pore-forming component remains elusive. Two of these genetically verified regulators are cyclophilin D (CypD) and the adenine nucleotide translocase (ANT) family. We investigated the ANT/CypD relationship in mPTP dynamics and I/R injury. Despite lacking all ANT isoforms, Ca 2+ -dependent mPTP opening persisted in cardiac mitochondria but was desensitized. This desensitization conferred resistance to I/R injury in ANT-deficient mice. CypD is hypothesized to trigger mPTP opening through isomerization of ANTs at proline-62. To test this, we generated mice that expressed a P62A mutated version of ANT1. These mice showed similar mPTP dynamics and I/R sensitivity as the wild type, indicating that P62 is dispensable for CypD regulation. Together, these data indicate that the ANT family contributes to mPTP opening independently of CypD.","journal":"Science Advances","year":2024,"id":428033,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"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":942244,"name":"Arielys Mendoza","orcid":"0000-0003-0137-0620","position":1,"is_corresponding":false},{"id":869610,"name":"Daniel Ramirez","orcid":"0009-0002-9582-3968","position":2,"is_corresponding":false},{"id":1171977,"name":"Dexter Robichaux","orcid":"0000-0002-4807-459X","position":3,"is_corresponding":false},{"id":289834,"name":"Jeffery D. Molkentin","orcid":"0000-0002-3558-6529","position":4,"is_corresponding":false},{"id":749958,"name":"Jason Karch","orcid":"0000-0002-3023-7469","position":5,"is_corresponding":false},{"id":1201234,"name":"Pooja Patel","orcid":"0000-0003-2513-8658","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T01:58:57.592578Z","pmid":"39661674","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":[]}