Recombinant human MG53 protein preserves mitochondria integrity in cardiomyocytes during ischemia reperfusion-induced oxidative stress

Abstract

Ischemic injury to the heart causes a loss of mitochondria function due to an increase in oxidative stress. MG53, also known as TRIM72, is highly expressed in striated muscle and is essential to repair damage to plasma membrane. We have shown that mg53-/-mice are more susceptible to ischemia-reperfusion injury, whereas treatment with exogenous recombinant human MG53 (rhMG53) reduces both infarct damage and restores cardiac function. This study assesses whether MG53 protects and repairs mitochondria injury after oxidative stress associated with myocardial infarction. We hypothesize that in addition to known cell membrane repair function, MG53 acts as a myokine to protect cardiomyocytes by maintaining mitochondrial function. A combination of in vivo and in vitro ischemia/reperfusion models were used to assess MG53's effect on mitochondria using biochemical assays and confocal microscopic imaging. Treatment with rhMG53 allowed cells to maintain a healthy mitochondrial membrane potential, reduced release of mitochondrial reactive oxygen species, and mitigated mitophagy. Mitochondrial localization of rhMG53 is mediated by exposure of and interaction with cardiolipin on the mitochondrial membrane. Our data demonstrates that rhMG53 protein preserves mitochondria integrity in cardiomyocytes during ischemia reperfusion-induced oxidative stress.