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- W2584268911 abstract "MG53 is a tripartite motif protein that is essential to plasma membrane regeneration. It binds to phosphatidylserine and facilitates the formation of repair patches at sites of plasma membrane disruption. Our previous studies have reported MG53's efficacy in ameliorating ischemia-reperfusion (I/R) injury to multiple organs including the heart, lungs, kidney, and brain. In I/R injury, mitochondria, however, are the primary victim of damage and the exposure of mitochondrial cardiolipin (CL) in response to I/R-induced oxidative stress procures cell death. Thus far, the role of MG53 in the preservation of mitochondrial function has not been studied. Here, we test the hypothesis that MG53 interacts with CL to protect mitochondria from oxidative stress. We find that mitochondria in the heart of MG53 knockout mouse are more susceptible to I/R injury than those of wild type mice. We also observe that MG53 targets mitochondria under chronic oxidative stress conditions, such as high-fat diet induced metabolic syndrome and amyotrophic lateral sclerosis. We demonstrate that MG53 binds to CL through a lipid dot-blot and a quantitative ELISA lipid-protein binding assay. Additionally, we show that exogenous recombinant human MG53 (rhMG53) protein can be up-taken by a variety of cells, including mesenchymal stem cells, human corneal epithelial cells, and valvular interstitial cells. Once internalized, rhMG53 translocates to mitochondria in response to oxidative stress induced by anoxia-reoxygenation treatment as revealed by live-cell imaging and 3D reconstruction of confocal microscopy. These data suggest that MG53 can target damaged mitochondria through a potential CL signaling mechanism and may implicate MG53 in mitochondrial membrane protection. To our knowledge, this study is the first to explore the interaction of MG53 with subcellular structures and provides a novel mechanism for MG53-mediated amelioration of I/R-induced tissue injury." @default.
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- W2584268911 date "2017-02-01" @default.
- W2584268911 modified "2023-09-29" @default.
- W2584268911 title "MG53 Interacts with Cardiolipin to Protect Mitochondria from Ischemia-Reperfusion Induced Oxidative Stress" @default.
- W2584268911 doi "https://doi.org/10.1016/j.bpj.2016.11.585" @default.
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