Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection.

In recent years, mitochondria have been recognized as regulators of cell death via both apoptosis and necrosis in addition to their essential role for cell survival. Cellular dysfunctions induced by intra- or extracellular insults converge on mitochondria and induce a sudden increase in permeability of the inner mitochondrial membrane, the so-called mitochondrial permeability transition. The mitochondrial permeability transition is caused by the opening of permeability transition pores (PTP) in the inner mitochondrial membrane with subsequent loss of ionic homeostasis, matrix swelling and outer membrane rupture. The detailed molecular mechanisms underlying the PTP-induced cellular dysfunction during cardiac pathology such as ischemia/reperfusion or post-infarction remodeling remain to be elucidated. However, a growing body of evidence supports the concept that pharmacological inhibition of the PTP is an effective and promising strategy for the protection of the heart against ischemia/reperfusion injury and for attenuation of the remodeling process which contributes to heart failure. This review summarizes and discusses current data on i) the structure and function of the PTP, ii) possible mechanisms and consequences of PTP opening and iii) the inhibition of PTP opening as a therapeutic approach for treatment of heart disease.