The mitochondrial permeability transition pore and cyclophilin D in cardioprotection

Mitochondria play a central role in heart energy metabolism and Ca 2+ homeostasis and are involved in the pathogenesis of many forms of heart disease. The body of knowledge on mitochondrial pathophysiology in living cells and organs is increasing, and so is the interest in mitochondria as potential...

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Published in:Biochimica et biophysica acta 2011-07, Vol.1813 (7), p.1316-1322
Main Authors: Di Lisa, Fabio, Carpi, Andrea, Giorgio, Valentina, Bernardi, Paolo
Format: Article
Language:English
Subjects:
Animals
Calcium
Cardioprotection
Cardiotonic Agents - metabolism
Cell Death
Cyclophilin A - metabolism
Cyclophilin D
Cyclophilins - metabolism
Energy Metabolism
Heart
Heart Diseases - drug therapy
Humans
Mice
Mitochondria
Mitochondria, Heart - metabolism
Mitochondrial Membrane Transport Proteins - metabolism
Mitochondrial Permeability Transition Pore
Myocardial Reperfusion Injury - metabolism
Peptidyl-Prolyl Isomerase F
Permeability transition
Reactive Oxygen Species - metabolism
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Summary:Mitochondria play a central role in heart energy metabolism and Ca 2+ homeostasis and are involved in the pathogenesis of many forms of heart disease. The body of knowledge on mitochondrial pathophysiology in living cells and organs is increasing, and so is the interest in mitochondria as potential targets for cardioprotection. This critical review will focus on the permeability transition pore (PTP) and its regulation by cyclophilin (CyP) D as effectors of endogenous protective mechanisms and as potential drug targets. The complexity of the regulatory interactions underlying control of mitochondrial function in vivo is beginning to emerge, and although apparently contradictory findings still exist we believe that the network of regulatory protein interactions involving the PTP and CyPs in physiology and pathology will increase our repertoire for therapeutic interventions in heart disease. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. ► The permeability transition pore (PTP) is an inner membrane mitochondrial channel. ► Cyclosporin (Cs) A inhibits the pore through Cyclophilin (CyP) D, a matrix protein. ► The PTP is a major target for cardioprotection through CyPD inhibition. ► CyPD regulates other mitochondrial functions in a CsA-sensitive manner. ► We focus on PTP regulation by CyPD as a drug target for cardioprotection.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/j.bbamcr.2011.01.031