Mitochondrial ca(2+) signaling and cardiac apoptosis.
The broad significance of apoptosis in the cardiovascular system only began to be recognized more widely recently. Apoptotic cell death is a normal component of postnatal morphogenesis of the human cardiac conduction system and may also be involved in the pathogenesis of a variety of cardiovascular diseases, including heart failure, myocardial infarction and atherosclerosis. Recently, it has become evident that mitochondria play important role in the signaling machinery of apoptotic cell death by releasing several apoptotic factors such as cytochrome c, apoptosis-inducing factor and procaspases. Furthermore, calcium signals have been identified as one of the major signals that converge on mitochondria to trigger the mitochondrion-dependent pathway of the apoptotic cell death. Calcium signals are also important in the physiological control of mitochondrial energy metabolism and it has not yet been explored how Ca(2+) turns from a signal for life to a signal for death. Since large elevations of cytosolic [Ca(2+)] ([Ca(2+)](c)) occur during each heartbeat in cardiac myocytes and these [Ca(2+)](c) signals may efficiently propagate to the mitochondria, the Ca(2+)-dependent mitochondrial pathways of apoptosis can be particularly important in the heart. This review is concerned with the role of mitochondrial Ca(2+) signaling in the control of cardiac apoptosis.
Pacher
P
P
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pa., USA.
Csordás
G
G
Hajnóczky
G
G
D017209:Apoptosis; D020013:Calcium Signaling; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D003574:Cytochrome c Group; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases