CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complex
Abstract The pathogenesis of myocardial ischemia-reperfusion injury (MIRI) is not fully clear. This study aims to investigate the role of mitochondrial-associated endoplasmic reticulum membrane (MAM)-related calcium overload in mitophagy. In vitro and in vivo models were established to simulate MIRI...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-07977-5 |
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| author | Bi-Ying Liu Zhao-Hui Dai Li Mao Ling-Zhi Guo Zhong-Bao Yang |
| author_facet | Bi-Ying Liu Zhao-Hui Dai Li Mao Ling-Zhi Guo Zhong-Bao Yang |
| author_sort | Bi-Ying Liu |
| collection | DOAJ |
| description | Abstract The pathogenesis of myocardial ischemia-reperfusion injury (MIRI) is not fully clear. This study aims to investigate the role of mitochondrial-associated endoplasmic reticulum membrane (MAM)-related calcium overload in mitophagy. In vitro and in vivo models were established to simulate MIRI. Cellular injury, apoptosis and mitophagy were measured and gene expression was analysized. The expression levels of glucose-regulated protein 75 (GRP75), receptor for inositol 1,4,5-trisphosphate (IP3R3), voltage-dependent anion-selective channel 1 (VDAC1), and calmodulin (CaM) and the mitochondrial calcium content, mitophagy and apoptosis were significantly increased in MIRI or hypoxia/reoxygenation (H/R) cells when compared to controls, but the mitochondrial membrane potential and ATP significantly decreased. GRP75 knockdown significantly inhibited CaM expression, mitochondrial calcium overload and mitophagy of H9C2 cells, whereas had no significant effect on IP3R3 and VDAC1 expression. CaM knockdown had no significant effect on the expression of GRP75, IP3R3 and VDAC1, and on mitochondrial calcium concentration, ATP levels and mitochondrial membrane potential of H9C2 cells, but significantly inhibited mitophagy and apoptosis. Collectively, these data suggest that the IP3R3-GRP75-VDAC1/CaM axis plays an important role in mitochondrial autophagy injury during myocardial ischemia-reperfusion and that it is a potential target for MIRI treatment. |
| format | Article |
| id | doaj-art-5db0db819da84edaa52028621abc4da3 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-5db0db819da84edaa52028621abc4da32025-08-20T03:37:31ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-07977-5CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complexBi-Ying Liu0Zhao-Hui Dai1Li Mao2Ling-Zhi Guo3Zhong-Bao Yang4Department of Basic Medicine, Changsha Health Vocational CollegeChest Pain Center of Changsha, The Affiliated Changsha Hospital of Hunan Normal UniversityDepartment of Basic Medicine, Changsha Health Vocational CollegeAcupuncture Rehabilitation department, Changsha Hospital of Tranditional Chinese MedicineChest Pain Center of Changsha, The Affiliated Changsha Hospital of Hunan Normal UniversityAbstract The pathogenesis of myocardial ischemia-reperfusion injury (MIRI) is not fully clear. This study aims to investigate the role of mitochondrial-associated endoplasmic reticulum membrane (MAM)-related calcium overload in mitophagy. In vitro and in vivo models were established to simulate MIRI. Cellular injury, apoptosis and mitophagy were measured and gene expression was analysized. The expression levels of glucose-regulated protein 75 (GRP75), receptor for inositol 1,4,5-trisphosphate (IP3R3), voltage-dependent anion-selective channel 1 (VDAC1), and calmodulin (CaM) and the mitochondrial calcium content, mitophagy and apoptosis were significantly increased in MIRI or hypoxia/reoxygenation (H/R) cells when compared to controls, but the mitochondrial membrane potential and ATP significantly decreased. GRP75 knockdown significantly inhibited CaM expression, mitochondrial calcium overload and mitophagy of H9C2 cells, whereas had no significant effect on IP3R3 and VDAC1 expression. CaM knockdown had no significant effect on the expression of GRP75, IP3R3 and VDAC1, and on mitochondrial calcium concentration, ATP levels and mitochondrial membrane potential of H9C2 cells, but significantly inhibited mitophagy and apoptosis. Collectively, these data suggest that the IP3R3-GRP75-VDAC1/CaM axis plays an important role in mitochondrial autophagy injury during myocardial ischemia-reperfusion and that it is a potential target for MIRI treatment.https://doi.org/10.1038/s41598-025-07977-5Myocardial ischemia reperfusion injury (MIRI)IP3R3-GRP75-VDAC1 complexCaMMitochondrial calcium overloadMitophagy |
| spellingShingle | Bi-Ying Liu Zhao-Hui Dai Li Mao Ling-Zhi Guo Zhong-Bao Yang CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complex Scientific Reports Myocardial ischemia reperfusion injury (MIRI) IP3R3-GRP75-VDAC1 complex CaM Mitochondrial calcium overload Mitophagy |
| title | CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complex |
| title_full | CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complex |
| title_fullStr | CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complex |
| title_full_unstemmed | CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complex |
| title_short | CaM promotes cardiomyocyte mitophagy in myocardial ischemia-reperfusion injury involving in the regulation of the IP3R3-GRP75-VDAC1 complex |
| title_sort | cam promotes cardiomyocyte mitophagy in myocardial ischemia reperfusion injury involving in the regulation of the ip3r3 grp75 vdac1 complex |
| topic | Myocardial ischemia reperfusion injury (MIRI) IP3R3-GRP75-VDAC1 complex CaM Mitochondrial calcium overload Mitophagy |
| url | https://doi.org/10.1038/s41598-025-07977-5 |
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