The mitochondrial permeability transition pore: molecular nature and role as a target in cardioprotection

J Mol Cell Cardiol. 2015 Jan:78:100-6. doi: 10.1016/j.yjmcc.2014.09.023. Epub 2014 Sep 28.

Abstract

The mitochondrial permeability transition (PT) - an abrupt increase permeability of the inner membrane to solutes - is a causative event in ischemia-reperfusion injury of the heart, and the focus of intense research in cardioprotection. The PT is due to opening of the PT pore (PTP), a high conductance channel that is critically regulated by a variety of pathophysiological effectors. Very recent work indicates that the PTP forms from the F-ATP synthase, which would switch from an energy-conserving to an energy-dissipating device. This review provides an update on the current debate on how this transition is achieved, and on the PTP as a target for therapeutic intervention. This article is part of a Special Issue entitled "Mitochondria: from basic mitochondrial biology to cardiovascular disease".

Keywords: Ischemia–reperfusion injury; Mitochondria; Permeability transition pore.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology
  • Cyclophilins / metabolism
  • Cyclosporine / pharmacology
  • Humans
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism*
  • Mitochondrial Membrane Transport Proteins / metabolism*
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Permeability Transition Pore
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Peptidyl-Prolyl Isomerase F
  • Permeability / drug effects

Substances

  • Cardiotonic Agents
  • Peptidyl-Prolyl Isomerase F
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Cyclosporine
  • Mitochondrial Proton-Translocating ATPases
  • Cyclophilins