Mitochondria-assisted cell suicide: a license to kill.
Although the mechanisms that underlie cardiac cell death remain cryptic, there is emerging evidence that mitochondria may play a pivotal role in this process. The mitochondrion initially deemed the "power house " is now considered to be a central integration site for biological signals that promote cell life or cell death. Since mitochondria contain the necessary apoptotic machinery to activate the cell-death pathway, it is now appreciated that mitochondria play a key decision-making role in whether a cell will live or die following a noxious signal-literally a "license to kill ". Permeability changes to the outer mitochondrial membrane, collapse of membrane potential, permeability pore complex assembly, release of cytotoxic proteins and caspase activation are associated with the mitochondrial-death pathway. Members of the Bcl-2 gene family can promote or suppress cell death by modulating mitochondrial function. Activation of the mitochondrial-death pathway has been reported in several cardiac pathologies and believed to account for the reported apoptosis observed in these disease entities. Given the meager and limited ability of cardiac muscle for repair or self-renewal after injury, the inordinate loss of cardiac cells is considered to be a key underlying factor in ventricular remodeling and decline in ventricular performance in patients with ischemic heart disease or post-myocardial infarction. This review will provide mechanistic insight into the involvement and contribution of the mitochondrion as a regulator of cell death in health and disease with particular focus on the heart.
Regula
Kelly M
KM
The Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Rm. 3016, 351 Taché Avenue, Winnipeg, Manitoba, R2H 2A6, Canada
Ens
Karen
K
Kirshenbaum
Lorrie A
LA
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D006331:Heart Diseases / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D008954:Models, Biological; D032342:Muscle Cells / Q000378:metabolism; D009203:Myocardial Infarction; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2