Heart mitochondria: gates of life and death.
Mitochondria are important generators of energy, providing ATP through oxidative phosphorylation. However, mitochondria also monitor complex information from the environment and intracellular milieu, including the presence or absence of growth factors, oxygen, reactive oxygen species, and DNA damage. Mitochondria have been implicated in the loss of cells in various cardiac pathologies, including ischaemia/reperfusion injury, cardiomyopathy, and congestive heart failure. The release of factors such as cytochrome c, Smac, Omi/Htr2A, and AIF from mitochondria serves to activate a highly complex and regulated cell death program. Furthermore, mitochondrial calcium overload might trigger opening of the mitochondrial permeability transition pore, causing uncoupling of oxidative phosphorylation, swelling of the mitochondria due to influx of water, and rupture of the mitochondrial outer membrane. In this review, we discuss the role of mitochondria in the control of cell death in cardiac myocytes.
Gustafsson
Asa B
AB
BioScience Center San Diego State University 5500 Campanile Drive San Diego, CA 92182-4650, USA. agustafs@sciences.sdsu.edu
Gottlieb
Roberta A
RA
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium