The 'mitochondrial permeability transition', characterized by a sudden induced change of the inner mitochondrial membrane permeability for water as well as for small substances (</=1.5 kDa), has been known for three decades. Research interest in the entity responsible for this phenomenon, the 'mitochondrial permeability transition pore' (mPTP), has dramatically increased after demonstration tha...

Ischemia-associated oxidative damage leading to necrosis is a major cause of catastrophic tissue loss, and elucidating its signaling mechanism is therefore of paramount importance. p53 is a central stress sensor responding to multiple insults, including oxidative stress to orchestrate apoptotic and autophagic cell death. Whether p53 can also activate oxidative stress-induced necrosis is, howeve...

Mitochondrial-mediated oxidative stress and apoptosis play a crucial role in neurodegenerative disease and aging. Both mitochondrial permeability transition (PT) and swelling of mitochondria have been involved in neurodegeneration. Indeed, knockout mice for cyclophilin-D (Cyc-D), a key regulatory component of the PT pore (PTP) that triggers mitochondrial swelling, resulted to be protected in pr...

Mitochondrial ATP generation by oxidative phosphorylation combines the stepwise oxidation by the electron transport chain (ETC) of the reducing equivalents NADH and FADH2 with the generation of ATP by the ATP synthase. Recent studies show that the ATP synthase is not only essential for the generation of ATP but may also contribute to the formation of the mitochondrial permeability transition po...

After a brief review of the early history of mitochondrial electrophysiology, the contribution of this approach to the study of the mitochondrial permeability transition (MPT) is recapitulated. It has for example provided evidence for a dimeric nature of the MPT pore, allowed the distinction between two levels of control of its activity, and underscored the relevance of redox events for the phe...

BACKGROUND Transient (low-conductance) opening of the mitochondrial permeability transition pore (mPTP) may limit mitochondrial calcium load and mediate mitochondrial reactive oxygen species (ROS) signaling. We hypothesize that transient mPTP opening and ROS mediate the protection associated with myocardial preconditioning and mitochondrial uncoupling. METHODS AND RESULTS Isolated perfused ra...

A large body of experimental evidence indicates that during an acute myocardial infarction (AMI), tissue injury occurring after reperfusion represents a significant amount of the whole, irreversible damage. It is now recognized that mitochondrial permeability transition pore opening plays a crucial role in this specific component of myocardial infarction. Ischaemic postconditioning and cyclospo...

The permeability transition (PT) denotes an increase of the mitochondrial inner membrane permeability to solutes with molecular masses up to about 1500 Da. It is presumed to be mediated by opening of a channel, the permeability transition pore (PTP), whose molecular nature remains a mystery. Here I briefly review the history of the PTP, discuss existing models, and present our new results indic...

Mitochondrial ATP generation by oxidative phosphorylation combines the stepwise oxidation by the electron transport chain (ETC) of the reducing equivalents NADH and FADH2 with the generation of ATP by the ATP synthase. Recent studies show that the ATP synthase is not only essential for the generation of ATP but may also contribute to the formation of the mitochondrial permeability transition po...

The mitochondrial permeability transition pore (MPTP) describes an inducible activity that regulates solute exchange between mitochondrial matrix contents and the surrounding cytoplasm, which acutely leads to loss of mitochondrial inner membrane potential but eventually organelle swelling and rupture. Mitochondrial rupture due to prolonged MPTP engagement, which is often the result of ischemic ...