Cyclophilin D: knocking on death's door.
Two recent genetic studies have identified a critical role for cyclophilin D, a component of the mitochondrial membrane permeability transition pore, in cell death induced by calcium, reactive oxygen species, and cardiac ischemia-reperfusion injury. Transgenic mice lacking cyclophilin D developed normally but showed reduced infarct size after coronary artery ligation and reperfusion. Cells from the knockout mice were resistant to death imposed by excess calcium and H2O2, but not to death from x-irradiation, staurosporine, tumor necrosis factor-alpha, or forced expression of proapoptotic proteins. These data raise questions about the relationship between apoptotic and necrotic cell death, and they also highlight cyclophilin D as a potential therapeutic target in myocardial infarction.
Schneider
Michael D
MD
Department of Medicine, Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA. michaels@bcm.tmc.edu
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D000226:Mitochondrial ADP, ATP Translocases / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D009336:Necrosis; D050994:Voltage-Dependent Anion Channels / Q000502:physiology
D000081406:Peptidyl-Prolyl Isomerase F; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C000631446:PPIF protein, mouse; D050994:Voltage-Dependent Anion Channels; D000226:Mitochondrial ADP, ATP Translocases; D021983:Cyclophilins