MG53 preserves mitochondrial integrity of cardiomyocytes during ischemia reperfusion-induced oxidative stress
Kristyn Gumpper-Fedus,
Ki Ho Park,
Hanley Ma,
Xinyu Zhou,
Zehua Bian,
Karthikeyan Krishnamurthy,
Matthew Sermersheim,
Jingsong Zhou,
Tao Tan,
Lei Li,
Jianxun Liu,
Pei-Hui Lin,
Hua Zhu,
Jianjie Ma
Affiliations
Kristyn Gumpper-Fedus
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Ki Ho Park
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Hanley Ma
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Xinyu Zhou
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Zehua Bian
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Karthikeyan Krishnamurthy
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Matthew Sermersheim
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Jingsong Zhou
University of Texas at Arlington, Department of Kinesiology, Arlington, TX, 76109, USA
Tao Tan
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Lei Li
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China
Jianxun Liu
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China
Pei-Hui Lin
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA
Hua Zhu
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA; Corresponding authors. 460 W 12th Avenue, Columbus, OH, 43210, USA.
Jianjie Ma
The Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, 43210, USA; Corresponding authors. 460 W 12th Avenue, Columbus, OH, 43210, USA.
Ischemic injury to the heart induces mitochondrial dysfunction due to increasing oxidative stress. MG53, also known as TRIM72, is highly expressed in striated muscle, is secreted as a myokine after exercise, and is essential for repairing damaged plasma membrane of many tissues by interacting with the membrane lipid phosphatidylserine (PS). We hypothesized MG53 could preserve mitochondrial integrity after an ischemic event by binding to the mitochondrial-specific lipid, cardiolipin (CL), for mitochondria protection to prevent mitophagy. Fluorescent imaging and Western blotting experiments showed recombinant human MG53 (rhMG53) translocated to the mitochondria after ischemic injury in vivo and in vitro. Fluorescent imaging indicated rhMG53 treatment reduced superoxide generation in ex vivo and in vitro models. Lipid-binding assay indicated MG53 binds to CL. Transfecting cardiomyocytes with the mitochondria-targeted mt-mKeima showed inhibition of mitophagy after MG53 treatment. Overall, we show that rhMG53 treatment may preserve cardiac function by preserving mitochondria in cardiomyocytes. These findings suggest MG53's interactions with mitochondria could be an attractive avenue for developing MG53 as a targeted protein therapy for cardioprotection.
