Mitochondrial Permeability Transition

Dear Colleagues,

For mitochondria to fulfill their bioenergetic function, mitochondrial inner membrane permeability needs to be tightly regulated. According to the fourth postulate of the chemiosmotic hypothesis, the inner membrane is a “specialised coupling membrane which has a low permeability to protons and to anions and cations generally” (Mitchell, P. Chemiosmotic coupling in oxidative and photosynthetic phosphorylation, Glynn Research, Bodmin Cornwall, England 1966, reprinted in Biochim Biophys Acta 2011, 1807, 1507-1538). This allows harnessing of the proton gradient through ATP synthase, completing the final step of oxidative phosphorylation. The mitochondrial permeability transition (mPT) is a reversible permeability increase of the inner membrane that can be triggered by matrix Ca²⁺. Initially considered an in vitro artifact, today the mPT is considered to be a regulated process mediated by opening of a high-conductance channel, the permeability transition pore (PTP). The PTP is currently investigated both as a physiological process involved in modulation of mitochondrial function and as a central event leading to disruption of cellular energy metabolism and cell death. As a pathological event, the mPT has been implicated as a central cause of cell damage in many conditions, including stroke, heart ischemia-reperfusion injury, muscular dystrophies and neurodegenerative diseases. Recent breakthrough discoveries have been made that significantly advance our understanding of the mPT. At the same time, these discoveries led to increasing appreciation of the tremendous complexity of the mPT, to the generation of new exciting theories and to new challenges, which are the matter of a lively debate. This Special Issue will focus on current progress in understanding the molecular mechanisms and pathophysiological role of this multifaceted phenomenon. We hope that it will serve as a platform for the exchange of new ideas and that it will further stimulate the development of the field.

Prof. Paolo Bernardi
Dr. Evgeny V. Pavlov
Guest Editors

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• permeability transition pore
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• cyclophilin D