tailieunhanh - Báo cáo khoa học: The mitochondrial permeability transition from in vitro artifact to disease target

The mitochondrial permeability transition pore is a high conductance chan-nel whose opening leads to an increase of mitochondrial inner membrane permeability to solutes with molecular masses up to 1500 Da. In this review we trace the rise of the permeability transition pore from the status ofin vitro artifact to that of effector mechanism of cell death. | ềFEBS Journal REVIEW ARTICLE The mitochondrial permeability transition from in vitro artifact to disease target Paolo Bernardi1 Alexandra Krauskopf1 Emy Basso1 Valeria Petronilli1 Elizabeth Blalchy-Dyson2 Fabio Di Lisa3 and Michael A. Forte2 1 Department of BiomedicalSciences and CNR Institute of Neurosciences University of Padova Italy 2 Vollum Institute L474 Oregon Health and Sciences University Portland OR USA 3 Department of BiologicalChemistry and CNR Institute of Neurosciences University of Padova Italy Keywords apoptosis calcium cancer cell death degenerative diseases drugs mitochondria necrosis permeability transition Correspondence P. Bernardi Department of Biomedical Sciences University of Padova Viale Giuseppe Colombo 3 I-35121 Padova Italy Fax 39 049 827 6361 E-mail bernardi@ The mitochondrial permeability transition pore is a high conductance channel whose opening leads to an increase of mitochondrial inner membrane permeability to solutes with molecular masses up to w 1500 Da. In this review we trace the rise of the permeability transition pore from the status of in vitro artifact to that of effector mechanism of cell death. We then cover recent results based on genetic inactivation of putative permeability transition pore components and discuss their meaning for our understanding of pore structure. Finally we discuss evidence indicating that the permeability transition pore plays a role in pathophysiology with specific emphasis on in vivo models of disease. Present address Center for Integrative Genomics University of Lausanne 1015 Lausanne-Dorigny Switzerland Received 6 January 2006 revised 1 March 2006 accepted 3 March 2006 doi Introduction The mitochondrial permeability transition PT is an increase of mitochondrial inner membrane permeability to solutes with molecular masses up to w 1500 Da. Under the conditions used in most in vitro studies PT is accompanied by depolarization matrix swelling depletion