Journal
FEBS LETTERS
Volume 584, Issue 10, Pages 1989-1996Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2010.02.022
Keywords
Permeability transition pore; Cyclophilin D; Apoptosis; Channel; Kinase; Chaperone
Funding
- Italian Ministry for University and Research
- Telethon-Italy
- AIRC
- NIH-PHS (USA)
- University of Padova
- Fondazione Cariparo
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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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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