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Physiol Rev. 2015 Oct;95(4):1111-55. doi: 10.1152/physrev.00001.2015.

The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology.

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Department of Biomedical Sciences and Consiglio Nazionale delle Ricerche Neuroscience Institute, University of Padova, Padova, Italy; Vollum Institute, Oregon Health and Sciences University, Portland, Oregon; and Department of Food Science, University of Udine, Udine, Italy.


The mitochondrial permeability transition (PT) is a permeability increase of the inner mitochondrial membrane mediated by a channel, the permeability transition pore (PTP). After a brief historical introduction, we cover the key regulatory features of the PTP and provide a critical assessment of putative protein components that have been tested by genetic analysis. The discovery that under conditions of oxidative stress the F-ATP synthases of mammals, yeast, and Drosophila can be turned into Ca(2+)-dependent channels, whose electrophysiological properties match those of the corresponding PTPs, opens new perspectives to the field. We discuss structural and functional features of F-ATP synthases that may provide clues to its transition from an energy-conserving into an energy-dissipating device as well as recent advances on signal transduction to the PTP and on its role in cellular pathophysiology.

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