CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor
Summary: CPNE5, a member of the Copine family, is characterized by its membrane-binding properties and functions as a regulatory modulator of intracellular signaling through the spatial redistribution of interacting protein partners. Emerging evidence has demonstrated that CPNE3 exerts cardioprotect...
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| Language: | English |
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Elsevier
2025-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225015639 |
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| author | Tingting Zhao Yangjinming Bai Yudong Fei Zhixing Wei Pengcheng Yao Qianji Che Yichao Zhang Ji Yan Kaiyan Chen Zhengyang Wu Junhao Qiu Yuepeng Wang Wei Li Qian Wang Yigang Li |
| author_facet | Tingting Zhao Yangjinming Bai Yudong Fei Zhixing Wei Pengcheng Yao Qianji Che Yichao Zhang Ji Yan Kaiyan Chen Zhengyang Wu Junhao Qiu Yuepeng Wang Wei Li Qian Wang Yigang Li |
| author_sort | Tingting Zhao |
| collection | DOAJ |
| description | Summary: CPNE5, a member of the Copine family, is characterized by its membrane-binding properties and functions as a regulatory modulator of intracellular signaling through the spatial redistribution of interacting protein partners. Emerging evidence has demonstrated that CPNE3 exerts cardioprotective effects via anti-apoptotic activity in myocardial ischemia-reperfusion injury models. However, the functional role of CPNE5 in cardiac pathology remains unclear. In this study, the cardiac-specific overexpression of CPNE5 in mice improved cardiac function, reduced cellular apoptosis, and attenuated cardiac fibrosis in both transverse aortic constriction and ischemia-reperfusion models. Conversely, CPNE5 knockout mice exhibited opposite pathological phenotypes. Mechanistic studies revealed that CPNE5 retains FAS within the endoplasmic reticulum and promotes its degradation through the ER-phagy pathway. This process involves CPNE5’s interaction with the autophagy marker LC3 and CALCOCO1, a key receptor in the ER-lysosome-associated degradation (ERLAD) pathway. Collectively, these findings indicate that CPNE5 overexpression protects cardiomyocytes against FASL-induced apoptosis under stress and ischemic conditions. |
| format | Article |
| id | doaj-art-5d0e12e534064904bc646059c5d7a7ca |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-5d0e12e534064904bc646059c5d7a7ca2025-08-25T04:14:40ZengElsevieriScience2589-00422025-09-0128911330210.1016/j.isci.2025.113302CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptorTingting Zhao0Yangjinming Bai1Yudong Fei2Zhixing Wei3Pengcheng Yao4Qianji Che5Yichao Zhang6Ji Yan7Kaiyan Chen8Zhengyang Wu9Junhao Qiu10Yuepeng Wang11Wei Li12Qian Wang13Yigang Li14Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, ChinaDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China; Corresponding authorDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China; Corresponding authorSummary: CPNE5, a member of the Copine family, is characterized by its membrane-binding properties and functions as a regulatory modulator of intracellular signaling through the spatial redistribution of interacting protein partners. Emerging evidence has demonstrated that CPNE3 exerts cardioprotective effects via anti-apoptotic activity in myocardial ischemia-reperfusion injury models. However, the functional role of CPNE5 in cardiac pathology remains unclear. In this study, the cardiac-specific overexpression of CPNE5 in mice improved cardiac function, reduced cellular apoptosis, and attenuated cardiac fibrosis in both transverse aortic constriction and ischemia-reperfusion models. Conversely, CPNE5 knockout mice exhibited opposite pathological phenotypes. Mechanistic studies revealed that CPNE5 retains FAS within the endoplasmic reticulum and promotes its degradation through the ER-phagy pathway. This process involves CPNE5’s interaction with the autophagy marker LC3 and CALCOCO1, a key receptor in the ER-lysosome-associated degradation (ERLAD) pathway. Collectively, these findings indicate that CPNE5 overexpression protects cardiomyocytes against FASL-induced apoptosis under stress and ischemic conditions.http://www.sciencedirect.com/science/article/pii/S2589004225015639Rodent cardiologyRodent molecular biologyBiological sciences |
| spellingShingle | Tingting Zhao Yangjinming Bai Yudong Fei Zhixing Wei Pengcheng Yao Qianji Che Yichao Zhang Ji Yan Kaiyan Chen Zhengyang Wu Junhao Qiu Yuepeng Wang Wei Li Qian Wang Yigang Li CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor iScience Rodent cardiology Rodent molecular biology Biological sciences |
| title | CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor |
| title_full | CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor |
| title_fullStr | CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor |
| title_full_unstemmed | CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor |
| title_short | CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor |
| title_sort | cpne5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of fas receptor |
| topic | Rodent cardiology Rodent molecular biology Biological sciences |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225015639 |
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