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

J Mol Cell Cardiol. 2015 Jan;78:142-53. doi: 10.1016/j.yjmcc.2014.08.015. Epub 2014 Aug 27.

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".

Keywords: Apoptosis; Cell death; Ischemia reperfusion injury; Mitochondrial permeability transition pore, MPTP; Necrosis; Permeability transition pore, PTP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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

Substances

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