Review

Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species

Keith A Webster

Department of Molecular & Cellular Pharmacology and the Vascular Biology Institute, University of Miami Medical Center, 1600 NW 10th Avenue, RMSB 6038, Miami, FL 33101, USA.

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Email the corresponding author at kwebster@med.miami.edu

Published Online:23 Nov 2012https://doi.org/10.2217/fca.12.58

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Abstract

Excess generation of reactive oxygen species (ROS) and cytosolic calcium accumulation play major roles in the initiation of programmed cell death during acute myocardial infarction. Cell death may include necrosis, apoptosis and autophagy, and combinations thereof. During ischemia, calcium handling between the sarcoplasmic reticulum and myofilament is disrupted and calcium is diverted to the mitochondria causing swelling. Reperfusion, while essential for survival, reactivates energy transduction and contractility and causes the release of ROS and additional ionic imbalance. During acute ischemia–reperfusion, the principal death pathways are programmed necrosis and apoptosis through the intrinsic pathway, initiated by the opening of the mitochondrial permeability transition pore and outer mitochondrial membrane permeabilization, respectively. Despite intense investigation, the mechanisms of action and modes of regulation of mitochondrial membrane permeabilization are incompletely understood. Extrinsic apoptosis, necroptosis and autophagy may also contribute to ischemia–reperfusion injury. In this review, the roles of dysregulated calcium and ROS and the contributions of Bcl-2 proteins, as well as mitochondrial morphology in promoting mitochondrial membrane permeability change and the ensuing cell death during myocardial infarction are discussed.

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Vol. 8, No. 6

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Published online 23 November 2012

Published in print November 2012

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Financial & competing interests disclosure

Supported by National Institutes of Health grant HL44578 and by a WG Ross Chair in vascular biology.The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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