{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:36:19Z","timestamp":1792787779005,"version":"4.5.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"13-15","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Supporting start-up funds of National Natural Science Foundation of GDPH","award":["KY0120220511"],"award-info":[{"award-number":["KY0120220511"]}]},{"name":"Supporting funds of National Natural Science Foundation of GDPH","award":["KY0120220389"],"award-info":[{"award-number":["KY0120220389"]}]},{"name":"Guangdong Provincial Natural Science Foundation","award":["2025A1515012688"],"award-info":[{"award-number":["2025A1515012688"]}]},{"name":"GDPH High-level Full-time Talent Introduction Supporting Research Funds","award":["KY 0120220119"],"award-info":[{"award-number":["KY 0120220119"]}]},{"name":"Guangzhou Science and Technology Plan Foundation","award":["2024A04J10022"],"award-info":[{"award-number":["2024A04J10022"]}]},{"name":"Science and Technology Plan Fund of Heyuan City","award":["250314091471340"],"award-info":[{"award-number":["250314091471340"]}]},{"name":"National Natural Science Foundation of China","award":["82203963"],"award-info":[{"award-number":["82203963"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Radiation-induced lung injury (RILI) is a major dose-limiting complication of thoracic radiotherapy. Although mitochondrial damage has been implicated in RILI, the endogenous transcriptional programs that restore mitochondrial structure and bioenergetic function after irradiation remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      To identify radiation-sensitive mitochondrial regulators in type II alveolar epithelial cells (AT2), we integrated single-cell RNA sequencing data from irradiated lungs with weighted gene co-expression network analysis. Transcription factor prediction, multi-omics correlation analysis, and molecular docking were used to construct upstream regulatory networks. The functional relevance of the KLF9\u2013CHCHD10 axis was validated using mitochondrial ultrastructure analysis, oxygen consumption assays, apoptosis detection, gene expression profiling, and CHCHD10 loss- and gain-of-function experiments performed\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Single-cell transcriptomic profiling identified CHCHD10, a mitochondrial cristae-associated protein, as a central radiation-sensitive hub in AT2 cells. Irradiation reduced CHCHD10 expression and disrupted mitochondrial homeostasis, leading to mitochondrial fragmentation, impaired oxygen consumption, enhanced epithelial apoptosis, activation of the Ppia\u2013CD147 inflammatory signaling axis, and suppression of PPAR\u03b3-associated metabolic homeostasis. Mechanistically, KLF9 directly activated CHCHD10 transcription, whereas irradiation suppressed the KLF9\u2013CHCHD10 circuit. Restoration of this pathway by CHCHD10 overexpression or glucocorticoid intervention preserved mitochondrial cristae integrity, improved bioenergetic recovery, and enhanced epithelial cell survival.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      , lung-specific CHCHD10 knockdown aggravated radiation-induced parenchymal remodeling and fibrotic deposition and partially weakened the protective efficacy of glucocorticoids.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      This study defines a GC\u2013KLF9\u2013CHCHD10 axis that restores mitochondrial ultrastructure and bioenergetics after radiation, positioning mitochondrial resilience as an active epithelial protective program in RILI.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      45, 581\u2013595.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261470735","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:19:18Z","timestamp":1784773158000},"page":"581-595","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A Glucocorticoid\u2013KLF9\u2013CHCHD10 Axis Governs Mitochondrial Resilience in Radiation-Induced Lung Injury"],"prefix":"10.1177","volume":"45","author":[{"given":"Peixin","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunpeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Heyuan People\u2019s Hospital, Guangdong Provincial People\u2019s Hospital Heyuan Hospital, Heyuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengsi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2650-7286","authenticated-orcid":false,"given":"Shasha","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.124.319866"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.317869"},{"key":"e_1_3_2_4_1","volume-title":"GeneReviews((R))","author":"Ait-EL-Mkadem Saadi S","year":"1993","unstructured":"Ait-EL-Mkadem Saadi S, , Chaussenot A, , Bannwarth S, et al. 1993. CHCHD10-Related Disorders. In: Adam M.P, , Feldman J, , Mirzaa G.M, , Pagon R.A, , Wallace S.E, & Amemiya A (eds.) GeneReviews((R)). 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