The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology
Top Cited Papers
- 1 October 2015
- journal article
- review article
- Published by American Physiological Society in Physiological Reviews
- Vol. 95 (4), 1111-1155
- https://doi.org/10.1152/physrev.00001.2015
Abstract
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 Ca2+-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.Keywords
Funding Information
- Associazione Italiana per la Ricerca sul Cancro (Italian Assocation for Cancer Research) (IG 13392, IG 15863)
- Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, Research and Universities) (FIRB RBAP11S8C3 and PRIN 20107Z8XBW)
- Fondazione Telethon (GGP14037 and GPP14187)
- Università degli Studi di Padova (University of Padova) (CPDA123598)
- Office of Extramural Research, National Institutes of Health (OER) (R01GM069883 and R03DA033978-01)
This publication has 163 references indexed in Scilit:
- Hexokinase II knockdown results in exaggerated cardiac hypertrophy via increased ROS productionEMBO Molecular Medicine, 2012
- Inhibitors of mitochondrial Kv1.3 channels induce Bax/Bak‐independent death of cancer cellsEMBO Molecular Medicine, 2012
- Inhibition of permeability transition pore opening by mitochondrial STAT3 and its role in myocardial ischemia/reperfusionBasic Research in Cardiology, 2010
- Characteristics and possible functions of mitochondrial Ca2+ transport mechanismsBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2009
- Mechanisms of Acetaminophen-Induced Liver NecrosisPublished by Springer Science and Business Media LLC ,2009
- Post-translational modifications of ATP synthase in the heart: biology and functionJournal of Bioenergetics and Biomembranes, 2009
- Recent advances in stucture-functional studies of mitochondrial factor BJournal of Bioenergetics and Biomembranes, 2009
- Unregulated mitochondrial GSK3β activity results in NADH:Ubiquinone oxidoreductase deficiencyNeurotoxicity Research, 2008
- The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesisApoptosis, 2007
- Identification and Comparative Analysis of the Peptidyl-Prolylcis/transIsomerase Repertoires ofH. sapiens, D. melanogaster, C. elegans, S. cerevisiae and Sz. pombeComparative and Functional Genomics, 2005