Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury.

Abstract

The mitochondrial permeability transition is a key event in cell death. Intense research efforts have been focused on elucidating the molecular components of the mitochondrial permeability transition pore (mPTP) to improve the understanding and treatment of various pathologies, including neurodegenerative disorders, cancer and cardiac diseases. Several molecular factors have been proposed as core components of the mPTP; however, further investigation has indicated that these factors are among a wide range of regulators. Thus, the scientific community lacks a clear model of the mPTP. Here, we review the molecular factors involved in the regulation and formation of the mPTP. Furthermore, we propose that the mitochondrial ATP synthase, specifically its c subunit, is the central core component of the mPTP complex. Moreover, we discuss the involvement of the mPTP in ischemia and reperfusion as well as the results of clinical studies targeting the mPTP to ameliorate ischemia-reperfusion injury. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".

• Authors: Giampaolo Morciano, Carlotta Giorgi, Massimo Bonora, Silvia Punzetti, Rita Pavasini, Mariusz R Wieckowski, Gianluca Campo, Paolo Pinton
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 78 Pg. 142-53 (Jan 2015) ISSN: 1095-8584 [Electronic] England
• PMID: 25172387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Cardiotonic Agents
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Protein Subunits
• Reactive Oxygen Species
• Mitochondrial Proton-Translocating ATPases
• Calcium

Topics

• Animals
• Apoptosis
• Calcium (metabolism)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Humans
• Mitochondria, Heart (drug effects, metabolism)
• Mitochondrial Membrane Transport Proteins (antagonists & inhibitors, chemistry, metabolism)
• Mitochondrial Permeability Transition Pore
• Mitochondrial Proton-Translocating ATPases (chemistry, metabolism)
• Molecular Targeted Therapy
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Necrosis (metabolism)
• Protein Subunits (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction