Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis
Ca2+ overload and mitochondrial dysfunction play crucial roles in myocardial ischemia-reperfusion (I/R) injury. Piezo1, a mechanosensitive cation channel, is essential for intracellular Ca2+ homeostasis. The objective of this research was to explore the effects of Piezo1 on mitochondrial function du...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323172400449X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841542498061647872 |
|---|---|
| author | Honglin Xu Xin Chen Shangfei Luo Jintao Jiang Xianmei Pan Yu He Bo Deng Silin Liu Rentao Wan Liwen Lin Qiaorui Tan Xiaoting Chen Youfen Yao Bin He Yajuan An Jing Li |
| author_facet | Honglin Xu Xin Chen Shangfei Luo Jintao Jiang Xianmei Pan Yu He Bo Deng Silin Liu Rentao Wan Liwen Lin Qiaorui Tan Xiaoting Chen Youfen Yao Bin He Yajuan An Jing Li |
| author_sort | Honglin Xu |
| collection | DOAJ |
| description | Ca2+ overload and mitochondrial dysfunction play crucial roles in myocardial ischemia-reperfusion (I/R) injury. Piezo1, a mechanosensitive cation channel, is essential for intracellular Ca2+ homeostasis. The objective of this research was to explore the effects of Piezo1 on mitochondrial function during myocardial I/R injury. We showed that the expression of myocardial Piezo1 was elevated in the infracted area of I/R and cardiomyocyte-specific Piezo1 deficiency (Piezo1△Myh6) mice attenuated I/R by decreasing infarct size and cardiac dysfunction. Piezo1△Myh6 regulated mitochondrial fusion and fission to improve mitochondrial function and decrease inflammation and oxidative stress in vivo and in vitro. Mechanistically, myocardial Piezo1 knockout alleviated intracellular calcium overload to normalize calpain-associated mitochondrial homeostasis. Our findings indicated that Piezo1 depletion in cardiomyocytes partially restored mitochondrial homeostasis during cardiac ischemia/reperfusion (I/R) injury. This study suggests an innovative therapeutic strategy to alleviate cardiac I/R injury. |
| format | Article |
| id | doaj-art-c71388d53dec4bee8de7ede55aac0d72 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-c71388d53dec4bee8de7ede55aac0d722025-01-14T04:12:11ZengElsevierRedox Biology2213-23172025-02-0179103471Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasisHonglin Xu0Xin Chen1Shangfei Luo2Jintao Jiang3Xianmei Pan4Yu He5Bo Deng6Silin Liu7Rentao Wan8Liwen Lin9Qiaorui Tan10Xiaoting Chen11Youfen Yao12Bin He13Yajuan An14Jing Li15Innovation Research Center, Shandong University of Traditional Chinese Medicine, Jinan, 250307, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaInnovation Research Center, Shandong University of Traditional Chinese Medicine, Jinan, 250307, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710049, ChinaThe Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaInnovation Research Center, Shandong University of Traditional Chinese Medicine, Jinan, 250307, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, LS2 9JT, UK; Corresponding author. Lingnan Medical Research Center, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.Ca2+ overload and mitochondrial dysfunction play crucial roles in myocardial ischemia-reperfusion (I/R) injury. Piezo1, a mechanosensitive cation channel, is essential for intracellular Ca2+ homeostasis. The objective of this research was to explore the effects of Piezo1 on mitochondrial function during myocardial I/R injury. We showed that the expression of myocardial Piezo1 was elevated in the infracted area of I/R and cardiomyocyte-specific Piezo1 deficiency (Piezo1△Myh6) mice attenuated I/R by decreasing infarct size and cardiac dysfunction. Piezo1△Myh6 regulated mitochondrial fusion and fission to improve mitochondrial function and decrease inflammation and oxidative stress in vivo and in vitro. Mechanistically, myocardial Piezo1 knockout alleviated intracellular calcium overload to normalize calpain-associated mitochondrial homeostasis. Our findings indicated that Piezo1 depletion in cardiomyocytes partially restored mitochondrial homeostasis during cardiac ischemia/reperfusion (I/R) injury. This study suggests an innovative therapeutic strategy to alleviate cardiac I/R injury.http://www.sciencedirect.com/science/article/pii/S221323172400449XI/RPiezo1MitochondriaInflammationCalpainCardiomyocytes |
| spellingShingle | Honglin Xu Xin Chen Shangfei Luo Jintao Jiang Xianmei Pan Yu He Bo Deng Silin Liu Rentao Wan Liwen Lin Qiaorui Tan Xiaoting Chen Youfen Yao Bin He Yajuan An Jing Li Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis Redox Biology I/R Piezo1 Mitochondria Inflammation Calpain Cardiomyocytes |
| title | Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis |
| title_full | Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis |
| title_fullStr | Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis |
| title_full_unstemmed | Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis |
| title_short | Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis |
| title_sort | cardiomyocyte specific piezo1 deficiency mitigates ischemia reperfusion injury by preserving mitochondrial homeostasis |
| topic | I/R Piezo1 Mitochondria Inflammation Calpain Cardiomyocytes |
| url | http://www.sciencedirect.com/science/article/pii/S221323172400449X |
| work_keys_str_mv | AT honglinxu cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT xinchen cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT shangfeiluo cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT jintaojiang cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT xianmeipan cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT yuhe cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT bodeng cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT silinliu cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT rentaowan cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT liwenlin cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT qiaoruitan cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT xiaotingchen cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT youfenyao cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT binhe cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT yajuanan cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis AT jingli cardiomyocytespecificpiezo1deficiencymitigatesischemiareperfusioninjurybypreservingmitochondrialhomeostasis |