ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies
Abstract The ECHS1 (short-chain enoyl-CoA hydratase 1) gene is critical for mitochondrial fatty acid β-oxidation and branched-chain amino acid metabolism. Mutations in ECHS1 lead to severe mitochondrial dysfunction and are implicated in rare metabolic and neurodegenerative disorders. This review sum...
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| Format: | Article |
| Language: | English |
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BMC
2025-08-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03959-y |
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| author | Qiang Fu Rui Qiu Shang Li Yuxiang Qin Ziyi Lu Shanxin Liyao Zimo Yang Xiang Cheng Yuewen Chen Huan Xu Yong Cheng |
| author_facet | Qiang Fu Rui Qiu Shang Li Yuxiang Qin Ziyi Lu Shanxin Liyao Zimo Yang Xiang Cheng Yuewen Chen Huan Xu Yong Cheng |
| author_sort | Qiang Fu |
| collection | DOAJ |
| description | Abstract The ECHS1 (short-chain enoyl-CoA hydratase 1) gene is critical for mitochondrial fatty acid β-oxidation and branched-chain amino acid metabolism. Mutations in ECHS1 lead to severe mitochondrial dysfunction and are implicated in rare metabolic and neurodegenerative disorders. This review summarizes current understanding of how ECHS1 participates in key molecular processes, including energy metabolism, oxidative stress regulation, and apoptosis, and discusses its influence on mitochondrial function. It also highlights advances in experimental models, including mouse, Drosophila, and induced pluripotent stem cell (iPSC) -based systems, which have illuminated the gene’s physiological roles while revealing model-specific limitations. Therapeutic approaches, such as dietary interventions, gene therapy, enzyme replacement therapy, and stem cell therapy, are critically evaluated, emphasizing their potential and current challenges. Despite significant progress, gaps remain in understanding ECHS1’s tissue-specific and developmental-stage-specific functions. This review underscores the need for advanced human-relevant models and integrative technologies to address these gaps and foster the development of personalized treatments for ECHS1-related disorders. |
| format | Article |
| id | doaj-art-d70f7c38ee564a75b0abc8f94f4e8b16 |
| institution | DOAJ |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-d70f7c38ee564a75b0abc8f94f4e8b162025-08-20T03:06:05ZengBMCOrphanet Journal of Rare Diseases1750-11722025-08-0120111210.1186/s13023-025-03959-yECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategiesQiang Fu0Rui Qiu1Shang Li2Yuxiang Qin3Ziyi Lu4Shanxin Liyao5Zimo Yang6Xiang Cheng7Yuewen Chen8Huan Xu9Yong Cheng10Center on Translational Neuroscience, Institute of National Security, Minzu University of ChinaCenter on Translational Neuroscience, Institute of National Security, Minzu University of ChinaCollege of Life and Environmental Sciences, Minzu University of ChinaCollege of Life and Environmental Sciences, Minzu University of ChinaCollege of Life and Environmental Sciences, Minzu University of ChinaCollege of Life and Environmental Sciences, Minzu University of ChinaCollege of Life and Environmental Sciences, Minzu University of ChinaCollege of Life and Environmental Sciences, Minzu University of ChinaChinese Academy of Sciences Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Translational Research for Brain Diseases, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen – Hong Kong Institute of Brain Science – Shenzhen Fundamental Research InstitutionsDepartment of Clinical Laboratory, General Hospital of Xizang Military CommandCenter on Translational Neuroscience, Institute of National Security, Minzu University of ChinaAbstract The ECHS1 (short-chain enoyl-CoA hydratase 1) gene is critical for mitochondrial fatty acid β-oxidation and branched-chain amino acid metabolism. Mutations in ECHS1 lead to severe mitochondrial dysfunction and are implicated in rare metabolic and neurodegenerative disorders. This review summarizes current understanding of how ECHS1 participates in key molecular processes, including energy metabolism, oxidative stress regulation, and apoptosis, and discusses its influence on mitochondrial function. It also highlights advances in experimental models, including mouse, Drosophila, and induced pluripotent stem cell (iPSC) -based systems, which have illuminated the gene’s physiological roles while revealing model-specific limitations. Therapeutic approaches, such as dietary interventions, gene therapy, enzyme replacement therapy, and stem cell therapy, are critically evaluated, emphasizing their potential and current challenges. Despite significant progress, gaps remain in understanding ECHS1’s tissue-specific and developmental-stage-specific functions. This review underscores the need for advanced human-relevant models and integrative technologies to address these gaps and foster the development of personalized treatments for ECHS1-related disorders.https://doi.org/10.1186/s13023-025-03959-yECHS1 protein, humanMitochondrial diseasesFatty acids, volatileBeta-oxidationGenetic therapy |
| spellingShingle | Qiang Fu Rui Qiu Shang Li Yuxiang Qin Ziyi Lu Shanxin Liyao Zimo Yang Xiang Cheng Yuewen Chen Huan Xu Yong Cheng ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies Orphanet Journal of Rare Diseases ECHS1 protein, human Mitochondrial diseases Fatty acids, volatile Beta-oxidation Genetic therapy |
| title | ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies |
| title_full | ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies |
| title_fullStr | ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies |
| title_full_unstemmed | ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies |
| title_short | ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies |
| title_sort | echs1 pathogenic mechanisms experimental models and emerging therapeutic strategies |
| topic | ECHS1 protein, human Mitochondrial diseases Fatty acids, volatile Beta-oxidation Genetic therapy |
| url | https://doi.org/10.1186/s13023-025-03959-y |
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