Genetic dissection of the permeability transition pore.
The permeability transition pore (PTP) regulates the structural re-organization of mitochondria in response to changes in cellular Ca(2+) and is thought to be an important participant in mitochondrial responses to cell death signals. Although the proteins forming the PTP have yet to be rigorously identified, recent examination of the response of mitochondria, cells and tissues lacking putative components of the PTP have been reported. Studies on mitochondria lacking cyclophilin D (CyP-D) have proved that this protein is the target for PTP inhibition by CsA; yet they have also unequivocally demonstrated that the PTP can form and open in the absence of CyP-D. Likewise, studies in mice lacking the two adenine nucleotide translocators expressed in this species have shown that a functional PTP can form in the absence of these proteins. Thus, the inner mitochondrial membrane components of the PTP remain to be identified, and the absence of CyP-D may not preclude PTP opening in vivo--a finding that questions the conclusion that the PTP participates in cell death pathways only in response to a restricted set of challenges.
Forte
Michael
M
Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. forte@ohsu.edu
Bernardi
Paolo
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000502:physiology; D007473:Ion Channels / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D000226:Mitochondrial ADP, ATP Translocases / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D010539:Permeability; D015398:Signal Transduction
D000081406:Peptidyl-Prolyl Isomerase F; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C000631446:PPIF protein, mouse; D000226:Mitochondrial ADP, ATP Translocases; D021983:Cyclophilins; D002118:Calcium