{"doi":"10.1016/j.jbc.2025.110406","title":"PLK1-mediated PDHA1 phosphorylation drives mitochondrial dysfunction, mitophagy, and cancer progression in Cr(VI)-associated lung cancer","abstract":"Hexavalent chromium (Cr(VI)) is a class I environmental carcinogen that induces lung epithelial cell transformation and promotes lung cancer progression by altering cell cycle regulation and cellular energy metabolism. In this study, we investigated the role of polo-like kinase 1 (PLK1) in Cr(VI)-transformed (CrT) bronchial epithelial cells (BEAS-2B) and found that PLK1 expression was significantly upregulated in these cells, leading to impaired mitochondrial function and enhanced mitophagy, which in turn stimulated cell proliferation both in vitro and in vivo. Mechanistically, we demonstrated that PLK1 directly phosphorylates the pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) at Thr57, leading to its destabilization and disruption of pyruvate dehydrogenase complex (PDHc) integrity. This modification inhibits oxidative phosphorylation (OXPHOS) and induces mitochondrial dysfunction. Furthermore, mitochondrial dysfunction triggers mitophagy and accelerates PDHA1 degradation, establishing a positive feedback loop that amplifies mitochondrial impairment and mitophagy, ultimately promoting cancer cell proliferation. These findings underscore the pivotal role of PLK1 in Cr(VI)-associated cancer progression and offer new insights into potential therapeutic targets to inhibit Cr(VI)-induced tumorigenesis.","journal":"Journal of Biological Chemistry","year":2025,"id":521462,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":1378357,"name":"Peng Jia","orcid":"0000-0001-7079-2072","position":1,"is_corresponding":false},{"id":497889,"name":"Zhiguo Li","orcid":"0000-0002-6869-2766","position":2,"is_corresponding":false},{"id":979200,"name":"Xiongjian Rao","orcid":"0000-0001-5645-9994","position":3,"is_corresponding":false},{"id":567667,"name":"Derek B. Allison","orcid":"0000-0002-5119-2474","position":4,"is_corresponding":false},{"id":1077519,"name":"Qi Qiao","orcid":"0000-0003-1240-0506","position":5,"is_corresponding":false},{"id":1391800,"name":"Zhuangzhuang Zhang","orcid":"0000-0003-1482-904X","position":6,"is_corresponding":false},{"id":411938,"name":"Yifan Kong","orcid":"0000-0002-5650-8079","position":7,"is_corresponding":false},{"id":411940,"name":"Yanquan Zhang","orcid":"0000-0003-3527-9972","position":8,"is_corresponding":false},{"id":1129570,"name":"Ruixin Wang","orcid":"0000-0003-2624-1593","position":9,"is_corresponding":false},{"id":411941,"name":"Jinghui Liu","orcid":"0000-0002-9676-1538","position":10,"is_corresponding":false},{"id":919743,"name":"Xinyi Wang","orcid":"0000-0002-7389-6018","position":11,"is_corresponding":false},{"id":411937,"name":"Chaohao Li","orcid":"0000-0001-5975-3937","position":12,"is_corresponding":false},{"id":411939,"name":"Fengyi Mao","orcid":"0000-0001-7785-6606","position":13,"is_corresponding":false},{"id":787029,"name":"Qing Shao","orcid":"0000-0001-9433-1131","position":14,"is_corresponding":false},{"id":369267,"name":"Tianyan Gao","orcid":"0000-0003-1159-3625","position":15,"is_corresponding":false},{"id":411943,"name":"Xiaoqi Liu","orcid":"0000-0002-6613-1746","position":16,"is_corresponding":false},{"id":747532,"name":"Qiongsi Zhang","orcid":"0000-0002-6234-5034","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40544996","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":[]}