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Carnitine\u2013acylcarnitine translocase deficiency (CACTD) is a scarce autosomal recessive genetic disease and may result in patients\u2019 death due to heart arrest or respiratory insufficiency. However, the reasons and mechanism of CACTD inducing respiratory insufficiency have never been elucidated. Herein, we employed lipidomic techniques to create comprehensive lipidomic maps of entire lungs throughout both prenatal and postnatal developmental stages in mice. We found that the acylcarnitines manifested notable variations and coordinated the expression levels of carnitine\u2013acylcarnitine translocase (Cact) across these lung developmental stages.\n            <jats:italic>Cact<\/jats:italic>\n            -null mice were all dead with a symptom of respiratory distress and exhibited failed lung development. Loss of Cact resulted in an accumulation of palmitoyl-carnitine (C16-acylcarnitine) in the lungs and promoted the proliferation of mesenchymal progenitor cells. Mesenchymal cells with elevated C16-acylcarnitine levels displayed minimal changes in energy metabolism but, upon investigation, revealed an interaction with sterile alpha motif domain and histidine-aspartate domain-containing protein 1 (Samhd1), leading to decreased protein abundance and enhanced cell proliferation. Thus, our findings present a mechanism addressing respiratory distress in CACTD, offering a valuable reference point for both the elucidation of pathogenesis and the exploration of treatment strategies for neonatal respiratory distress.\n          <\/jats:p>","DOI":"10.34133\/research.0620","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T18:50:01Z","timestamp":1738349401000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":4,"title":["Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme Proliferation"],"prefix":"10.34133","volume":"8","author":[{"given":"Xing","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, \rInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China."},{"name":"School of Life Sciences, \rUniversity of Chinese Academy of Sciences, Beijing 100049, China."},{"name":"Department of Respiratory, \rChildren\u2019s Hospital of Nanjing Medical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin Man","family":"Lam","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, \rInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, \rInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China."},{"name":"School of Life Sciences, \rUniversity of Chinese Academy of Sciences, Beijing 100049, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesong","family":"Mo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular 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Sciences, Beijing 100049, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Long","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, \rInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China."},{"name":"School of Life Sciences, \rUniversity of Chinese Academy of Sciences, Beijing 100049, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, \rInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China."},{"name":"School of Life Sciences, \rUniversity of Chinese Academy of Sciences, Beijing 100049, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, \rInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China."},{"name":"School of Life Sciences, \rUniversity of Chinese Academy of Sciences, Beijing 100049, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Mei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, \rInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1621-9643","authenticated-orcid":true,"given":"Guanghou","family":"Shui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, \rInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China."},{"name":"School of Life Sciences, \rUniversity of Chinese Academy of Sciences, Beijing 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