Signal transduction to the permeability transition pore.
The permeability transition pore (PTP) is an inner mitochondrial membrane channel that has been thoroughly characterized functionally, yet remains an elusive molecular entity. The best characterized PTP-regulatory component, cyclophilin (CyP) D, is a matrix protein that favors pore opening. CyP inhibitors, CyP-D null animals, and in situ PTP readouts have established the role of PTP as an effector mechanism of cell death, and the growing definition of PTP signalling mechanisms. This review briefly covers the functional features of the PTP and the role played by its dysregulation in disease pathogenesis. Recent progress on PTP modulation by kinase/phosphatase signal transduction is discussed, with specific emphasis on hexokinase and on the Akt-ERK-GSK3 axis, which might modulate the PTP through CyP-D phosphorylation.
Rasola
Andrea
A
Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova, Italy. rasola@bio.unipd.it
Sciacovelli
Marco
M
Pantic
Boris
B
Bernardi
Paolo
P
D000818:Animals; D004194:Disease; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D015398:Signal Transduction
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore