Research Paper Volume 12, Issue 13 pp 13618—13632
The YAP/SERCA2a signaling pathway protects cardiomyocytes against reperfusion-induced apoptosis
- 1 Department of Cardiology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528308, Guangdong, China
- 2 Department of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China
- 3 Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528308, Guangdong, China
Received: February 24, 2020 Accepted: May 27, 2020 Published: July 9, 2020https://doi.org/10.18632/aging.103481
How to Cite
Copyright © 2020 Zhong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Mitochondria and the endoplasmic reticulum (ER) are known to promote cardiac ischemia/reperfusion (I/R) injury. Overexpression of yes-associated protein (YAP) and/or sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) has been shown to protect cardiomyocytes against I/R-induced injury. Here, we show that activation of the YAP/SERCA2a pathway attenuated mitochondrial damage and ER stress (ERS) to maintain cardiomyocyte viability in the setting of I/R injury. Our results demonstrate that I/R treatment reduced the transcription and expression of YAP and SERCA2a, along with a decline in cardiomyocyte viability. The overexpression of YAP promoted SERCA2a transcription, whereas SERCA2a upregulation did not affect the YAP transcription, suggesting that YAP functions upstream of SERCA2a. Activation of the YAP/SERCA2a pathway suppressed mitochondrial damage by sustaining the mitochondrial redox balance and restoring mitochondrial bioenergetics. Additionally, its activation repressed ERS, reduced calcium overload, and eventually blocked caspase activation. The knockdown of SERCA2a suppressed the protective effects of YAP overexpression on mitochondrial damage and ERS. Overall, our findings reveal that the YAP/SERCA2a pathway attenuates the mitochondrial damage and ERS in response to cardiac I/R injury by regulating the mitochondria–ER communication.