title: Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species.
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.
authors.affiliation: Department of Molecular & Cellular Pharmacology, University of Miami Medical Center, FL 33101, USA. kwebster@med.miami.edu
authors.forename: Keith A
authors.initials: KA
authors.lastname: Webster
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000032:analysis / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D003600:Cytosol / Q000737:chemistry; D006801:Humans; D051336:Mitochondrial Membranes / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D010539:Permeability; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species; D002118:Calcium