Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme Proliferation
Disruption of acylcarnitine homeostasis results in life-threatening outcomes in humans. Carnitine–acylcarnitine translocase deficiency (CACTD) is a scarce autosomal recessive genetic disease and may result in patients’ death due to heart arrest or respiratory insufficiency. However, the reasons and...
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0620 |
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| author | Xing Liu Sin Man Lam Yu Zheng Lesong Mo Muhan Li Tianyi Sun Xiaohui Long Shulin Peng Xinwei Zhang Mei Mei Guanghou Shui Shilai Bao |
| author_facet | Xing Liu Sin Man Lam Yu Zheng Lesong Mo Muhan Li Tianyi Sun Xiaohui Long Shulin Peng Xinwei Zhang Mei Mei Guanghou Shui Shilai Bao |
| author_sort | Xing Liu |
| collection | DOAJ |
| description | Disruption of acylcarnitine homeostasis results in life-threatening outcomes in humans. Carnitine–acylcarnitine translocase deficiency (CACTD) is a scarce autosomal recessive genetic disease and may result in patients’ 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–acylcarnitine translocase (Cact) across these lung developmental stages. Cact-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. |
| format | Article |
| id | doaj-art-1c6a6c52f7a44037a6337ed18d3fc47d |
| institution | OA Journals |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-1c6a6c52f7a44037a6337ed18d3fc47d2025-08-20T02:29:30ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0620Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme ProliferationXing Liu0Sin Man Lam1Yu Zheng2Lesong Mo3Muhan Li4Tianyi Sun5Xiaohui Long6Shulin Peng7Xinwei Zhang8Mei Mei9Guanghou Shui10Shilai Bao11State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.Disruption of acylcarnitine homeostasis results in life-threatening outcomes in humans. Carnitine–acylcarnitine translocase deficiency (CACTD) is a scarce autosomal recessive genetic disease and may result in patients’ 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–acylcarnitine translocase (Cact) across these lung developmental stages. Cact-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.https://spj.science.org/doi/10.34133/research.0620 |
| spellingShingle | Xing Liu Sin Man Lam Yu Zheng Lesong Mo Muhan Li Tianyi Sun Xiaohui Long Shulin Peng Xinwei Zhang Mei Mei Guanghou Shui Shilai Bao Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme Proliferation Research |
| title | Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme Proliferation |
| title_full | Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme Proliferation |
| title_fullStr | Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme Proliferation |
| title_full_unstemmed | Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme Proliferation |
| title_short | Palmitoyl-carnitine Regulates Lung Development by Promoting Pulmonary Mesenchyme Proliferation |
| title_sort | palmitoyl carnitine regulates lung development by promoting pulmonary mesenchyme proliferation |
| url | https://spj.science.org/doi/10.34133/research.0620 |
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