Research Paper Volume 12, Issue 5 pp 4474—4488
Irisin activates Opa1-induced mitophagy to protect cardiomyocytes against apoptosis following myocardial infarction
- 1 The First Center Clinic College of Tianjin Medical University, Tianjin First Center Hospital, Tianjin, China
- 2 Department of Cardiology, Tianjin First Center Hospital, Tianjin, China
received: October 18, 2019 ; accepted: March 2, 2020 ; published: March 10, 2020 ;https://doi.org/10.18632/aging.102899
How to Cite
Copyright © 2020 Xin and Lu. 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.
Myocardial infarction is characterized by sudden ischemia and cardiomyocyte death. Mitochondria have critical roles in regulating cardiomyocyte viability and can sustain damage under ischemic conditions. Mitophagy is a mechanism by which damaged mitochondria are removed by autophagy to maintain mitochondrial structure and function. We investigated the role of the dynamin-like GTPase optic atrophy 1 (Opa1) in mitophagy following myocardial infarction. Opa1 expression was downregulated in infarcted hearts in vivo and in hypoxia-treated cardiomyocytes in vitro. We found that Opa1 overexpression protected cardiomyocytes against hypoxia-induced damage and enhanced cell viability by inducing mitophagy. Opa1-induced mitophagy was activated by treatment with irisin, which protected cardiomyocytes from further damage following myocardial infarction. Opa1 knockdown abolished the cardioprotective effects of irisin resulting in an enhanced inflammatory response, increased oxidative stress, and mitochondrial dysfunction in cardiomyocytes. Our data indicate that Opa1 plays an important role in maintaining cardiomyocyte viability and mitochondrial function following myocardial infarction by inducing mitophagy. Irisin can activate Opa1-induced mitophagy and protect against cardiomyocyte injury following myocardial infarction.